Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Letters in Drug Design & Discovery
  4. Volume 21, Issue 14
  5. Article
Volume 21, Issue 14
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

In recent decades, the mortality and morbidity of Gastrointestinal (GI) cancer have remarkably increased, especially in younger individuals. Recent studies revealed that neuronal connections play an active part in GI tumor initiation and progression. Also, studies showed neurotransmitters and neuropeptides drive the activation of various oncogenic pathways downstream of neural receptors within cancer cells, underscoring the importance of neural signaling pathways in GI tumor malignancy. These studies show that the humoral and nervous pathways can transfer signals of tumors to the brain. But, the exact mechanism of this regulation from the brain to the gut is still unknown. In this review, we summarized the mechanism of the neuronal pathway in the regulation of promotion or suppression of GI cancer and oncogene activation, and we summarize recent findings linking the nervous system to GI tumor progression and highlight the importance of targeting neural mechanisms in GI tumor therapy.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/lddd/10.2174/0115701808258045231010102318
2024-11-01
2025-04-15

  • From This Site

    /content/journals/lddd/10.2174/0115701808258045231010102318
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. TorreL.A. BrayF. SiegelR.L. FerlayJ. Lortet-TieulentJ. JemalA. Global cancer statistics, 2012.CA Cancer J. Clin.20156528710810.3322/caac.21262 25651787
     [Google Scholar]
  2. BhargavaA. BunkarN. KhareN.K. MishraD. MishraP.K. Nanoengineered strategies to optimize dendritic cells for gastrointestinal tumor immunotherapy: From biology to translational medicine.Nanomedicine20149142187220210.2217/nnm.14.115 25405796
     [Google Scholar]
  3. HaddadP. MirM.R. JamaliM. AbdiradA. AlikhasiA. FarhanF. MemariF. SadighiS. ShahiF. Gastrointestinal tumor board: An evolving experience in Tehran Cancer Institute.Acta Med. Iran.2013514270273 23690109
     [Google Scholar]
  4. OndicovaK. MravecB. Role of nervous system in cancer aetiopathogenesis.Lancet Oncol.201011659660110.1016/S1470‑2045(09)70337‑7 20522385
     [Google Scholar]
  5. PetraA.I. PanagiotidouS. HatziagelakiE. StewartJ.M. ContiP. TheoharidesT.C. Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation.Clin. Ther.201537598499510.1016/j.clinthera.2015.04.002 26046241
     [Google Scholar]
  6. HolzerP. FarziA. Neuropeptides and the microbiota-gut-brain axis.Adv. Exp. Med. Biol.201481719521910.1007/978‑1‑4939‑0897‑4_9
     [Google Scholar]
  7. TsangS.W. AuyeungK.K. BianZ.X. KoJ.K. Pathogenesis, experimental models and contemporary pharmacotherapy of irritable bowel syndrome: Story about the brain-gut axis.Curr. Neuropharmacol.201614884285610.2174/1570159X14666160324144154 27009115
     [Google Scholar]
  8. OndicovaK. PecenákJ. MravecB. The role of the vagus nerve in depression.Neuroendocrinol. Lett.2010315602608 21173739
     [Google Scholar]
  9. SasselliV. PachnisV. BurnsA.J. The enteric nervous system.Dev. Biol.20123661647310.1016/j.ydbio.2012.01.012 22290331
     [Google Scholar]
  10. LasradoR. BoesmansW. KleinjungJ. PinC. BellD. BhawL. McCallumS. ZongH. LuoL. CleversH. Vanden BergheP. PachnisV. Lineage-dependent spatial and functional organization of the mammalian enteric nervous system.Science2017356633972272610.1126/science.aam7511 28522527
     [Google Scholar]
  11. BrookesS.J.H. SpencerN.J. CostaM. ZagorodnyukV.P. Extrinsic primary afferent signalling in the gut.Nat. Rev. Gastroenterol. Hepatol.201310528629610.1038/nrgastro.2013.29 23438947
     [Google Scholar]
  12. FurnessJ.B. CallaghanB.P. RiveraL.R. ChoH-J. The enteric nervous system and gastrointestinal innervation: Integrated local and central control.Adv. Exp. Med. Biol.20148173971
     [Google Scholar]
  13. FurnessJ.B. Types of neurons in the enteric nervous system.J. Auton. Nerv. Syst.2000811-3879610.1016/S0165‑1838(00)00127‑2 10869706
     [Google Scholar]
  14. BoesmansW. LasradoR. Vanden BergheP. PachnisV. Heterogeneity and phenotypic plasticity of glial cells in the mammalian enteric nervous system.Glia201563222924110.1002/glia.22746 25161129
     [Google Scholar]
  15. MorarachK. MikhailovaA. KnoflachV. MemicF. KumarR. LiW. ErnforsP. MarklundU. Diversification of molecularly defined myenteric neuron classes revealed by single-cell RNA sequencing.Nat. Neurosci.2021241344610.1038/s41593‑020‑00736‑x 33288908
     [Google Scholar]
  16. FungC. Vanden BergheP. Functional circuits and signal processing in the enteric nervous system.Cell. Mol. Life Sci.202077224505452210.1007/s00018‑020‑03543‑6 32424438
     [Google Scholar]
  17. RaoM. NelmsB.D. DongL. Salinas-RiosV. RutlinM. GershonM.D. CorfasG. Enteric glia express proteolipid protein 1 and are a transcriptionally unique population of glia in the mammalian nervous system.Glia201563112040205710.1002/glia.22876 26119414
     [Google Scholar]
  18. HallerA.v. On the Sensible and Irritable Parts of Animals.The Natural Philosophy of Albrecht von Haller1936
     [Google Scholar]
  19. UesakaT. YoungH.M. PachnisV. EnomotoH. Development of the intrinsic and extrinsic innervation of the gut.Dev. Biol.2016417215816710.1016/j.ydbio.2016.04.016 27112528
     [Google Scholar]
  20. LomaxA.E. SharkeyK.A. FurnessJ.B. The participation of the sympathetic innervation of the gastrointestinal tract in disease states.Neurogastroenterol. Motil.2010221718 19686308
     [Google Scholar]
  21. BrowningK.N. TravagliR.A. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions.Compr. Physiol.2014441339136810.1002/cphy.c130055 25428846
     [Google Scholar]
  22. WalterG.C. PhillipsR.J. BaronowskyE.A. PowleyT.L. Versatile, high-resolution anterograde labeling of vagal efferent projections with dextran amines.J. Neurosci. Methods200917811910.1016/j.jneumeth.2008.11.003 19056424
     [Google Scholar]
  23. BrierleyS. HughesP. HarringtonA. BlackshawL. Innervation of the gastrointestinal tract by spinal and vagal afferent nerves.Elsevier201210.1016/B978‑0‑12‑382026‑6.00024‑5
     [Google Scholar]
  24. HeffnerK.L. LovingT.J. RoblesT.F. Kiecolt-GlaserJ.K. Examining psychosocial factors related to cancer incidence and progression: In search of the silver lining.Brain Behav. Immun.200317110911110.1016/S0889‑1591(02)00076‑4 12615195
     [Google Scholar]
  25. BianchiM.T. SongL. ZhangH. MacdonaldR.L. Two different mechanisms of disinhibition produced by GABAA receptor mutations linked to epilepsy in humans.J. Neurosci.200222135321532710.1523/JNEUROSCI.22‑13‑05321.2002 12097483
     [Google Scholar]
  26. JansenA. HoepfnerM. HerzigK.H. RieckenE.O. ScherüblH. GABA C receptors in neuroendocrine gut cells: A new GABA-binding site in the gut.Pflugers Arch.20004412-329430010.1007/s004240000412 11211116
     [Google Scholar]
  27. GlassmeierG. HerzigK.H. HöpfnerM. LemmerK. JansenA. ScherüblH. Expression of functional GABA A receptors in cholecystokinin-secreting gut neuroendocrine murine STC-1 cells.J. Physiol.1998510380581410.1111/j.1469‑7793.1998.805bj.x 9660895
     [Google Scholar]
  28. SzczaurskaK. MazurkiewiczM. OpolskiA. The role of GABA-ergic system in carcinogenesis.Postepy Hig. Med. Dosw.2003575485500 14737966
     [Google Scholar]
  29. WatanabeM. MaemuraK. OkiK. ShiraishiN. ShibayamaY. KatsuK. Gamma-aminobutyric acid (GABA) and cell proliferation: Focus on cancer cells.Histol. Histopathol.2006211011351141 16835836
     [Google Scholar]
  30. MoonM.S. ChoE.W. ByunH.S. JungI.L. KimI.G. GAD 67KD antisense in colon cancer cells inhibits cell growth and sensitizes to butyrate and pH reduction and H2O2 and γ-radiation.Arch. Biochem. Biophys.2004430222923610.1016/j.abb.2004.07.015 15369822
     [Google Scholar]
  31. ZomotE. kanner, B.I. The interaction of the γ-aminobutyric acid transporter GAT-1 with the neurotransmitter is selectively impaired by sulfhydryl modification of a conformationally sensitive cysteine residue engineered into extracellular loop IV.J. Biol. Chem.200327844429504295810.1074/jbc.M209307200 12925537
     [Google Scholar]
  32. TatsutaM. IishiH. BabaM. NakaizumiA. UeharaH. TaniguchiH. Effect of gamma-butyrolactone on baclofen inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.Oncology199249212312610.1159/000227024 1574247
     [Google Scholar]
  33. SchullerH.M. Al-WadeiH.A.N. MajidiM. GABAB receptor is a novel drug target for pancreatic cancer.Cancer2008112476777810.1002/cncr.23231 18098271
     [Google Scholar]
  34. MaemuraK. ShiraishiN. SakagamiK. KawakamiK. InoueT. MuranoM. WatanabeM. OtsukiY. Proliferative effects of γ-aminobutyric acid on the gastric cancer cell line are associated with extracellular signal-regulated kinase 1/2 activation.J. Gastroenterol. Hepatol.200924468869610.1111/j.1440‑1746.2008.05687.x 19032445
     [Google Scholar]
  35. MazurkiewiczM. OpolskiA. WietrzykJ. RadzikowskiC. KleinrokZ. GABA level and GAD activity in human and mouse normal and neoplastic mammary gland.J. Experim. Clin. Can. Res.199918247253
     [Google Scholar]
  36. LiY.H. LiuY. LiY-D. LiuY-H. LiF. JuQ. XieP.L. LiG.C. GABA stimulates human hepatocellular carcinoma growth through overexpressed GABAA receptor theta subunit.World J. Gastroenterol.201218212704271110.3748/wjg.v18.i21.2704 22690081
     [Google Scholar]
  37. TakeharaA. HosokawaM. EguchiH. OhigashiH. IshikawaO. NakamuraY. NakagawaH. γ-aminobutyric acid (GABA) stimulates pancreatic cancer growth through overexpressing GABAA receptor π subunit.Cancer Res.200767209704971210.1158/0008‑5472.CAN‑07‑2099 17942900
     [Google Scholar]
  38. De PontiF. Pharmacology of serotonin: What a clinician should know.Gut200453101520153510.1136/gut.2003.035568 15361507
     [Google Scholar]
  39. GrinA. StreutkerC.J. Neuroendocrine tumors of the luminal gastrointestinal tract.Arch. Pathol. Lab. Med.2015139675075610.5858/arpa.2014‑0130‑RA 26030244
     [Google Scholar]
  40. CattaneoM.G. FesceR. VicentiniL.M. Mitogenic effect of serotonin in human small cell lung carcinoma cells via both 5-HT1A and 5-HT1D receptors.Eur. J. Pharmacol.1995291220921110.1016/0922‑4106(95)90145‑0 8566173
     [Google Scholar]
  41. TuttonP.J.M. BarklaD.H. The influence of serotonin on the mitotic rate in the colonic crypt epithelium and in colonic adenocarcinoma in rats.Clin. Exp. Pharmacol. Physiol.197851919410.1111/j.1440‑1681.1978.tb00657.x 25153
     [Google Scholar]
  42. Al‐WadeiH.A. SchullerH.M. Nicotinic receptor‐associated modulation of stimulatory and inhibitory neurotransmitters in NNK‐induced adenocarcinoma of the lungs and pancreas.J. Pathology200921843744510.1002/path.2542
     [Google Scholar]
  43. VicautE. LaemmelE. StückerO. Impact of serotonin on tumour growth.Ann. Med.200032318719410.3109/07853890008998826 10821326
     [Google Scholar]
  44. BaguleyB.C. ColeG. ThomsenL.L. ZhuangL. Serotonin involvement in the antitumour and host effects of flavone-8-acetic acid and 5,6-dimethylxanthenone-4-acetic acid.Cancer Chemother. Pharmacol.1993331778110.1007/BF00686027 8269593
     [Google Scholar]
  45. El-SalhyM. SitohyB. NorrgårdÖ. Triple therapy with octreotide, galanin, and serotonin reduces the size and blood vessel density and increases apoptosis of a rat colon carcinoma.Regul. Pept.20031111-314515210.1016/S0167‑0115(02)00280‑X 12609762
     [Google Scholar]
  46. SchaalC. PadmanabhanJ. ChellappanS. The role of nAChR and calcium signaling in pancreatic cancer initiation and progression.Cancers2015731447147110.3390/cancers7030845 26264026
     [Google Scholar]
  47. YangT. HeW. CuiF. XiaJ. ZhouR. WuZ. ZhaoY. ShiM. MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells.Oncotarget2016714180851809410.18632/oncotarget.7634 26919111
     [Google Scholar]
  48. RubíB. MaechlerP. Minireview: New roles for peripheral dopamine on metabolic control and tumor growth: let’s seek the balance.Endocrinology2010151125570558110.1210/en.2010‑0745 21047943
     [Google Scholar]
  49. BeaulieuJ.M. GainetdinovR.R. The physiology, signaling, and pharmacology of dopamine receptors.Pharmacol. Rev.201163118221710.1124/pr.110.002642 21303898
     [Google Scholar]
  50. BasuS. DasguptaP.S. Alteration of dopamine D2 receptors in human malignant stomach tissue.Dig. Dis. Sci.19974261260126410.1023/A:1018862309440 9201092
     [Google Scholar]
  51. KouX. HanY. YangD. LiuY. FuJ. ZhengS. HeD. ZhouL. ZengC. Dopamine d 1 -like receptors suppress proliferation of vascular smooth muscle cell induced by insulin-like growth factor-1.Clin. Exp. Hypertens.201436314014710.3109/10641963.2013.789048 23713966
     [Google Scholar]
  52. LengZ.G. LinS.J. WuZ.R. GuoY.H. CaiL. ShangH.B. TangH. XueY.J. LouM.Q. ZhaoW. LeW.D. ZhaoW.G. ZhangX. WuZ.B. Activation of DRD5 (dopamine receptor D5) inhibits tumor growth by autophagic cell death.Autophagy20171381404141910.1080/15548627.2017.1328347 28613975
     [Google Scholar]
  53. HuangH. WuK. MaJ. DuY. CaoC. NieY. Dopamine D2 receptor suppresses gastric cancer cell invasion and migration via inhibition of EGFR/AKT/MMP-13 pathway.Int. Immunopharmacol.20163911312010.1016/j.intimp.2016.07.002 27468100
     [Google Scholar]
  54. Moreno-SmithM. LeeS.J. LuC. NagarajaA.S. HeG. RupaimooleR. HanH.D. JenningsN.B. RohJ.W. NishimuraM. KangY. AllenJ.K. ArmaizG.N. MatsuoK. ShahzadM.M.K. Bottsford-MillerJ. LangleyR.R. ColeS.W. LutgendorfS.K. SiddikZ.H. SoodA.K. Biologic effects of dopamine on tumor vasculature in ovarian carcinoma.Neoplasia2013155502IN1510.1593/neo.121412 23633922
     [Google Scholar]
  55. HicklinD.J. EllisL.M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis.J. Clin. Oncol.20052351011102710.1200/JCO.2005.06.081 15585754
     [Google Scholar]
  56. CookeE. ZhouJ. WyseureT. JoshiS. BhatV. DurdenD. MosnierL. von DrygalskiA. Vascular permeability and remodelling coincide with inflammatory and reparative processes after joint bleeding in factor VIII-deficient mice.Thromb. Haemost.201811861036104710.1055/s‑0038‑1641755 29847841
     [Google Scholar]
  57. SarkarC. ChakrobortyD. ChowdhuryU.R. DasguptaP.S. BasuS. Dopamine increases the efficacy of anticancer drugs in breast and colon cancer preclinical models.Clin. Cancer Res.20081482502251010.1158/1078‑0432.CCR‑07‑1778 18413843
     [Google Scholar]
  58. LeeJ.W. ShahzadM.M.K. LinY.G. Armaiz-PenaG. MangalaL.S. HanH.D. KimH.S. NamE.J. JenningsN.B. HalderJ. NickA.M. StoneR.L. LuC. LutgendorfS.K. ColeS.W. LokshinA.E. SoodA.K. Surgical stress promotes tumor growth in ovarian carcinoma.Clin. Cancer Res.20091582695270210.1158/1078‑0432.CCR‑08‑2966 19351748
     [Google Scholar]
  59. YangE.V. SoodA.K. ChenM. LiY. EubankT.D. MarshC.B. JewellS. FlavahanN.A. MorrisonC. YehP.E. LemeshowS. GlaserR. Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells.Cancer Res.20066621103571036410.1158/0008‑5472.CAN‑06‑2496 17079456
     [Google Scholar]
  60. ShinV.Y. WuW.K.K. ChuK.M. KooM.W.L. WongH.P.S. LamE.K.Y. TaiE.K.K. ChoC.H. Functional role of β-adrenergic receptors in the mitogenic action of nicotine on gastric cancer cells.Toxicol. Sci.2006961212910.1093/toxsci/kfl118 17003101
     [Google Scholar]
  61. Al-WadeiH.A. Al-WadeiM.H. SchullerH.M. Prevention of pancreatic cancer by the beta-blocker propranolol.Anticancer Drugs200920647748210.1097/CAD.0b013e32832bd1e3 19387337
     [Google Scholar]
  62. CoelhoM. MozM. CorreiaG. TeixeiraA. MedeirosR. RibeiroL. Antiproliferative effects of β-blockers on human colorectal cancer cells.Oncol. Rep.20153352513252010.3892/or.2015.3874 25812650
     [Google Scholar]
  63. LiuX. WuW.K.K. YuL. SungJ.J.Y. SrivastavaG. ZhangS.T. ChoC.H. Epinephrine stimulates esophageal squamous-cell carcinoma cell proliferation via β-adrenoceptor-dependent transactivation of extracellular signal-regulated kinase/cyclooxygenase-2 pathway.J. Cell. Biochem.20081051536010.1002/jcb.21802 18452159
     [Google Scholar]
  64. OtaniY. KubotaT. SakuraiY. IgarashiN. YokoyamaT. KimataM. WadaN. KameyamaK. KumaiK. OkadaY. KitajimaM. Expression of matrix metalloproteinases in gastric carcinoma and possibility of clinical application of matrix metalloproteinase inhibitor in vivo.Ann. N. Y. Acad. Sci.19998781 INHIBITION OF54154310.1111/j.1749‑6632.1999.tb07721.x 10415767
     [Google Scholar]
  65. ShiM. LiuD. DuanH. HanC. WeiB. QianL. ChenC. GuoL. HuM. YuM. SongL. ShenB. GuoN. Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer.Mol. Cancer20109126910.1186/1476‑4598‑9‑269 20939893
     [Google Scholar]
  66. ValèsS. BacolaG. BiraudM. TouvronM. BessardA. GeraldoF. DoughertyK.A. LashaniS. BossardC. FlamantM. DuchalaisE. Marionneau-LambotS. OullierT. OliverL. NeunlistM. ValletteF.M. Van LandeghemL. Tumor cells hijack enteric glia to activate colon cancer stem cells and stimulate tumorigenesis.EBioMedicine20194917218810.1016/j.ebiom.2019.09.045 31662289
     [Google Scholar]
  67. WangD. FuL. SunH. GuoL. DuBoisR.N. Prostaglandin E2 promotes colorectal cancer stem cell expansion and metastasis in mice.Gastroenterology20151491884189510.1053/j.gastro.2015.07.064
     [Google Scholar]
  68. PesicM. GretenF.R. Inflammation and cancer: Tissue regeneration gone awry.Curr. Opin. Cell Biol.201643556110.1016/j.ceb.2016.07.010 27521599
     [Google Scholar]
  69. LiebigC. AyalaG. WilksJ.A. BergerD.H. AlboD. Perineural invasion in cancer.Cancer2009115153379339110.1002/cncr.24396 19484787
     [Google Scholar]
  70. DuchalaisE. GuilluyC. NedellecS. TouvronM. BessardA. TouchefeuY. BossardC. BoudinH. LouarnG. NeunlistM. Van LandeghemL. Colorectal cancer cells adhere to and migrate along the neurons of the enteric nervous system.Cell. Mol. Gastroenterol. Hepatol.201851314910.1016/j.jcmgh.2017.10.002 29188232
     [Google Scholar]
  71. GershonM.D. BursztajnS. Properties of the enteric nervous system: Limitation of access of intravascular macromolecules to the myenteric plexus and muscularis externa.J. Comp. Neurol.1978180346748710.1002/cne.901800305 659670
     [Google Scholar]
  72. YangZ. ChenY. WeiX. WuD. MinZ. QuanY. Upregulated NTF4 in colorectal cancer promotes tumor development via regulating autophagy.Int. J. Oncol.20205661442145410.3892/ijo.2020.5027 32236587
     [Google Scholar]
  73. DrewesJ.L. CoronaA. SanchezU. FanY. HouriganS.K. WeidnerM. Transmission and clearance of potential procarcinogenic bacteria during fecal microbiota transplantation for recurrent Clostridioides difficile.JCI Insight2019410.1172/jci.insight.130848
     [Google Scholar]
  74. BullmanS. PedamalluC.S. SicinskaE. ClancyT.E. ZhangX. CaiD. NeubergD. HuangK. GuevaraF. NelsonT. ChipashviliO. HaganT. WalkerM. RamachandranA. DiosdadoB. SernaG. MuletN. LandolfiS. Ramon y CajalS. FasaniR. AguirreA.J. NgK. ÉlezE. OginoS. TaberneroJ. FuchsC.S. HahnW.C. NuciforoP. MeyersonM. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer.Science201735863691443144810.1126/science.aal5240 29170280
     [Google Scholar]
  75. HuybrechtsI. ZouiouichS. LoobuyckA. VandenbulckeZ. VogtmannE. PisanuS. IguacelI. ScalbertA. IndaveI. SmelovV. GunterM.J. MichelsN. The human microbiome in relation to cancer risk: A systematic review of epidemiologic studies.Cancer Epidemiol. Biomarkers Prev.202029101856186810.1158/1055‑9965.EPI‑20‑0288 32727720
     [Google Scholar]
  76. TomkovichS. DejeaC.M. WingleeK. DrewesJ.L. ChungL. HousseauF. PopeJ.L. GauthierJ. SunX. MühlbauerM. LiuX. FathiP. AndersR.A. BesharatiS. Perez-ChanonaE. YangY. DingH. WuX. WuS. WhiteJ.R. GharaibehR.Z. FodorA.A. WangH. PardollD.M. JobinC. SearsC.L. Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic.J. Clin. Invest.201912941699171210.1172/JCI124196 30855275
     [Google Scholar]
  77. LiuT. ZhangL. JooD. SunS-C. NF-κB signaling in inflammation.Signal Transduct. Target. Ther.2017219
     [Google Scholar]
  78. FeltonJ. ChengK. ShangA.C. HuS. LarabeeS.M. DrachenbergC.B. Two sides to colon cancer: Mice mimic human anatomical region disparity in colon cancer development and progression.J. Cancer. Metast. Treatm.20184
     [Google Scholar]
  79. BergstromK. ShanX. CaseroD. BatushanskyA. LagishettyV. JacobsJ.P. HooverC. KondoY. ShaoB. GaoL. ZandbergW. NoyovitzB. McDanielJ.M. GibsonD.L. PakpourS. KazemianN. McGeeS. HouchenC.W. RaoC.V. GriffinT.M. SonnenburgJ.L. McEverR.P. BraunJ. XiaL. Proximal colon–derived O-glycosylated mucus encapsulates and modulates the microbiota.Science2020370651546747210.1126/science.aay7367 33093110
     [Google Scholar]
  80. VaesN. LentjesM.H.F.M. GijbelsM.J. RademakersG. DaenenK.L. BoesmansW. WoutersK.A.D. GeuzensA. QuX. SteinbuschH.P.J. RuttenB.P.F. BaldwinS.H. SharkeyK.A. HofstraR.M.W. van EngelandM. Vanden BergheP. MelotteV. NDRG4, an early detection marker for colorectal cancer, is specifically expressed in enteric neurons.Neurogastroenterol. Motil.2017299e1309510.1111/nmo.13095 28524415
     [Google Scholar]
  81. BeneshE.C. MillerP.M. PfaltzgraffE.R. Grega-LarsonN.E. HagerH.A. SungB.H. QuX. BaldwinH.S. WeaverA.M. BaderD.M. Bves and NDRG4 regulate directional epicardial cell migration through autocrine extracellular matrix deposition.Mol. Biol. Cell201324223496351010.1091/mbc.e12‑07‑0539 24048452
     [Google Scholar]
  82. FontenasL. De SantisF. Di DonatoV. DegernyC. ChambraudB. Del BeneF. TawkM. Neuronal Ndrg4 is essential for nodes of ranvier organization in zebrafish.PLoS Genet.20161211e100645910.1371/journal.pgen.1006459 27902705
     [Google Scholar]
  83. GarciaS.B. AranhaA.L. GarciaF.R.B. BasileF.V. PintoA.P.M. OliveiraE.C. ZucolotoS. A retrospective study of histopathological findings in 894 cases of megacolon: what is the relationship between megacolon and colonic cancer?Rev. Inst. Med. Trop.2003452919310.1590/S0036‑46652003000200007 12754574
     [Google Scholar]
  84. VespúcioM.V.O. TurattiA. ModianoP. OliveiraE.C. ChicoteS.R.M. PintoA.M.P. GarciaS.B. Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen.Braz. J. Med. Biol. Res.200841431131710.1590/S0100‑879X2008005000008 18297187
     [Google Scholar]
  85. KoS.Y. DassC.R. NurgaliK. Netrin-1 in the developing enteric nervous system and colorectal cancer.Trends Mol. Med.201218954455410.1016/j.molmed.2012.07.001 22920895
     [Google Scholar]
  86. CastetsM. BroutierL. MolinY. BrevetM. ChazotG. GadotN. PaquetA. MazelinL. Jarrosson-WuillemeL. ScoazecJ.Y. BernetA. MehlenP. DCC constrains tumour progression via its dependence receptor activity.Nature2012482738653453710.1038/nature10708 22158121
     [Google Scholar]
  87. MazelinL. BernetA. Bonod-BidaudC. PaysL. ArnaudS. GespachC. BredesenD.E. ScoazecJ.Y. MehlenP. Netrin-1 controls colorectal tumorigenesis by regulating apoptosis.Nature20044317004808410.1038/nature02788 15343335
     [Google Scholar]
  88. MehlenP. FurneC. Netrin-1: When a neuronal guidance cue turns out to be a regulator of tumorigenesis.Cell. Mol. Life Sci.200562222599261610.1007/s00018‑005‑5191‑3 16158190
     [Google Scholar]
  89. GodlewskiJ. ŁakomyI.M. Changes in vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide and neuropeptide Y-ergic structures of the enteric nervous system in the carcinoma of the human large intestine.Folia Histochem. Cytobiol.201048220821610.2478/v10042‑010‑0052‑9 20675276
     [Google Scholar]
  90. GodlewskiJ. KaleczycJ. Somatostatin, substance P and calcitonin gene-related peptide-positive intramural nerve structures of the human large intestine affected by carcinoma.Folia Histochem. Cytobiol.201048347548310.2478/v10042‑010‑0079‑y 21071356
     [Google Scholar]
  91. GodlewskiJ. PidsudkoZ. Characteristic of galaninergic components of the enteric nervous system in the cancer invasion of human large intestine.Ann. Anat.2012194436837210.1016/j.aanat.2011.11.009 22226150
     [Google Scholar]
  92. RaufmanJ.P. SamimiR. ShahN. KhuranaS. ShantJ. DrachenbergC. XieG. WessJ. ChengK. Genetic ablation of M3 muscarinic receptors attenuates murine colon epithelial cell proliferation and neoplasia.Cancer Res.200868103573357810.1158/0008‑5472.CAN‑07‑6810 18483237
     [Google Scholar]
  93. ChengK. ShangA.C. DrachenbergC.B. ZhanM. RaufmanJ.P. Differential expression of M3 muscarinic receptors in progressive colon neoplasia and metastasis.Oncotarget2017813211062111410.18632/oncotarget.15500 28416748
     [Google Scholar]
  94. XieG. ChengK. ShantJ. RaufmanJ.P. Acetylcholine-induced activation of M 3 muscarinic receptors stimulates robust matrix metalloproteinase gene expression in human colon cancer cells.Am. J. Physiol. Gastrointest. Liver Physiol.20092964G755G76310.1152/ajpgi.90519.2008 19221016
     [Google Scholar]
  95. RaufmanJ.P. ChengK. SaxenaN. ChahdiA. BeloA. KhuranaS. XieG. Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells.Biochem. Biophys. Res. Commun.2011415231932410.1016/j.bbrc.2011.10.052 22027145
     [Google Scholar]
  96. RaufmanJ.P. DawsonP.A. RaoA. DrachenbergC.B. HeathJ. ShangA.C. HuS. ZhanM. PolliJ.E. ChengK. Slc10a2 -null mice uncover colon cancer-promoting actions of endogenous fecal bile acids.Carcinogenesis201536101193120010.1093/carcin/bgv107 26210740
     [Google Scholar]
  97. ChengK. MetryM. FeltonJ. ShangA.C. DrachenbergC.B. XuS. ZhanM. SchumacherJ. GuoG.L. PolliJ.E. RaufmanJ.P. Diminished gallbladder filling, increased fecal bile acids, and promotion of colon epithelial cell proliferation and neoplasia in fibroblast growth factor 15-deficient mice.Oncotarget2018939255722558510.18632/oncotarget.25385 29876009
     [Google Scholar]
  98. RenzB.W. TanakaT. SunagawaM. TakahashiR. JiangZ. MacchiniM. DantesZ. ValentiG. WhiteR.A. MiddelhoffM.A. IlmerM. ObersteinP.E. AngeleM.K. DengH. HayakawaY. WestphalenC.B. WernerJ. RemottiH. ReichertM. TailorY.H. NagarK. FriedmanR.A. IugaA.C. OliveK.P. WangT.C. Cholinergic Signaling via muscarinic receptors directly and indirectly suppresses pancreatic tumorigenesis and cancer stemness.Cancer Discov.20188111458147310.1158/2159‑8290.CD‑18‑0046 30185628
     [Google Scholar]
  99. ZahalkaA.H. FrenetteP.S. Nerves in cancer.Nat. Rev. Cancer202020314315710.1038/s41568‑019‑0237‑2 31974491
     [Google Scholar]
  100. Cervantes-VillagranaR.D. Albores-GarcíaD. Cervantes-VillagranaA.R. García-AcevezS.J. Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies.Signal Transduct. Target. Ther.2020519910.1038/s41392‑020‑0205‑z 32555170
     [Google Scholar]
  101. ZahalkaA.H. Arnal-EstapéA. MaryanovichM. NakaharaF. CruzC.D. FinleyL.W.S. FrenetteP.S. Adrenergic nerves activate an angio-metabolic switch in prostate cancer.Science2017358636132132610.1126/science.aah5072 29051371
     [Google Scholar]
  102. MauffreyP. TchitchekN. BarrocaV. BemelmansA.P. FirlejV. AlloryY. RoméoP.H. MagnonC. Progenitors from the central nervous system drive neurogenesis in cancer.Nature2019569775867267810.1038/s41586‑019‑1219‑y 31092925
     [Google Scholar]
  103. MagnonC. HallS.J. LinJ. XueX. GerberL. FreedlandS.J. FrenetteP.S. Autonomic nerve development contributes to prostate cancer progression.Science20133416142123636110.1126/science.1236361 23846904
     [Google Scholar]
  104. RogerE. MartelS. Bertrand-ChapelA. DepollierA. ChuvinN. PommierR.M. YacoubK. CaligarisC. Cardot-RuffinoV. ChauvetV. AiresS. MohkamK. MabrutJ.Y. AdhamM. FenouilT. HervieuV. BroutierL. CastetsM. NeuzilletC. CassierP.A. TomasiniR. SentisS. BartholinL. Schwann cells support oncogenic potential of pancreatic cancer cells through TGFβ signaling.Cell Death Dis.2019101288610.1038/s41419‑019‑2116‑x 31767842
     [Google Scholar]
  105. DebordeS. OmelchenkoT. LyubchikA. ZhouY. HeS. McNamaraW.F. ChernichenkoN. LeeS.Y. BarajasF. ChenC.H. BakstR.L. VakianiE. HeS. HallA. WongR.J. Schwann cells induce cancer cell dispersion and invasion.J. Clin. Invest.201612641538155410.1172/JCI82658 26999607
     [Google Scholar]
  106. OkadaY. EiblG. GuhaS. DuffyJ.P. ReberH.A. HinesO.J. Nerve growth factor stimulates MMP-2 expression and activity and increases invasion by human pancreatic cancer cells.Clin. Exp. Metastasis200421428529210.1023/B:CLIN.0000046131.24625.54 15554384
     [Google Scholar]
  107. OkadaY. EiblG. DuffyJ.P. ReberH.A. HinesO.J. Glial cell-derived neurotrophic factor upregulates the expression and activation of matrix metalloproteinase-9 in human pancreatic cancer.Surgery2003134229329910.1067/msy.2003.239 12947332
     [Google Scholar]
  108. MiknyoczkiS.J. LangD. HuangL. Klein-SzantoA.J.P. DionneC.A. RuggeriB.A. Neurotrophins and Trk receptors in human pancreatic ductal adenocarcinoma: Expression patterns and effects on In vitro invasive behavior.Int. J. Cancer199981341742710.1002/(SICI)1097‑0215(19990505)81:3<417:AID‑IJC16>3.0.CO;2‑6 10209957
     [Google Scholar]
  109. AlbiniA. Tumor and endothelial cell invasion of basement membranes.Pathol. Oncol. Res.19984323024110.1007/BF02905254 9761943
     [Google Scholar]
  110. BiankinA.V. WaddellN. KassahnK.S. GingrasM.C. MuthuswamyL.B. JohnsA.L. MillerD.K. WilsonP.J. PatchA.M. WuJ. ChangD.K. CowleyM.J. GardinerB.B. SongS. HarliwongI. IdrisogluS. NourseC. NourbakhshE. ManningS. WaniS. GongoraM. PajicM. ScarlettC.J. GillA.J. PinhoA.V. RoomanI. AndersonM. HolmesO. LeonardC. TaylorD. WoodS. XuQ. NonesK. Lynn FinkJ. ChristA. BruxnerT. CloonanN. KolleG. NewellF. PineseM. Scott MeadR. HumphrisJ.L. KaplanW. JonesM.D. ColvinE.K. NagrialA.M. HumphreyE.S. ChouA. ChinV.T. ChantrillL.A. MawsonA. SamraJ.S. KenchJ.G. LovellJ.A. DalyR.J. MerrettN.D. ToonC. EpariK. NguyenN.Q. BarbourA. ZepsN. KakkarN. ZhaoF. QingWu Y.; Wang, M.; Muzny, D.M.; Fisher, W.E.; Charles Brunicardi, F.; Hodges, S.E.; Reid, J.G.; Drummond, J.; Chang, K.; Han, Y.; Lewis, L.R.; Dinh, H.; Buhay, C.J.; Beck, T.; Timms, L.; Sam, M.; Begley, K.; Brown, A.; Pai, D.; Panchal, A.; Buchner, N.; De Borja, R.; Denroche, R.E.; Yung, C.K.; Serra, S.; Onetto, N.; Mukhopadhyay, D.; Tsao, M.S.; Shaw, P.A.; Petersen, G.M.; Gallinger, S.; Hruban, R.H.; Maitra, A.; Iacobuzio-Donahue, C.A.; Schulick, R.D.; Wolfgang, C.L.; Morgan, R.A.; Lawlor, R.T.; Capelli, P.; Corbo, V.; Scardoni, M.; Tortora, G.; Tempero, M.A.; Mann, K.M.; Jenkins, N.A.; Perez-Mancera, P.A.; Adams, D.J.; Largaespada, D.A.; Wessels, L.F.A.; Rust, A.G.; Stein, L.D.; Tuveson, D.A.; Copeland, N.G.; Musgrove, E.A.; Scarpa, A.; Eshleman, J.R.; Hudson, T.J.; Sutherland, R.L.; Wheeler, D.A.; Pearson, J.V.; McPherson, J.D.; Gibbs, R.A.; Grimmond, S.M. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.Nature2012491742439940510.1038/nature11547 23103869
     [Google Scholar]
  111. MulliganL.M. GDNF and the RET receptor in cancer: New insights and therapeutic potential.Front. Physiol.20199187310.3389/fphys.2018.01873 30666215
     [Google Scholar]
  112. JurcakN.R. RuckiA.A. MuthS. ThompsonE. SharmaR. DingD. Axon guidance molecules promote perineural invasion and metastasis of orthotopic pancreatic tumors in mice.Gastroenterology2019157338385010.1053/j.gastro.2019.05.065
     [Google Scholar]
  113. FoleyK. RuckiA.A. XiaoQ. ZhouD. LeubnerA. MoG. KleponisJ. WuA.A. SharmaR. JiangQ. AndersR.A. Iacobuzio-DonahueC.A. HajjarK.A. MaitraA. JaffeeE.M. ZhengL. Semaphorin 3D autocrine signaling mediates the metastatic role of annexin A2 in pancreatic cancer.Sci. Signal.20158388ra77ra7710.1126/scisignal.aaa5823 26243191
     [Google Scholar]
  114. SinhaS. FuY.Y. GrimontA. KetchamM. LafaroK. SaglimbeniJ.A. AskanG. BaileyJ.M. MelchorJ.P. ZhongY. JooM.G. Grbovic-HuezoO. YangI.H. BasturkO. BakerL. ParkY. KurtzR.C. TuvesonD. LeachS.D. PasrichaP.J. PanIN neuroendocrine cells promote tumorigenesis via neuronal cross-talk.Cancer Res.20177781868187910.1158/0008‑5472.CAN‑16‑0899 28386018
     [Google Scholar]
  115. DemirI.E. CeyhanG.O. LieblF. D’HaeseJ.G. MaakM. FriessH. Neural invasion in pancreatic cancer: The past, present and future.Cancers2010231513152710.3390/cancers2031513 24281170
     [Google Scholar]
  116. GriffinN. FaulknerS. JoblingP. HondermarckH. Targeting neurotrophin signaling in cancer: The renaissance.Pharmacol. Res.2018135121710.1016/j.phrs.2018.07.019 30031169
     [Google Scholar]
  117. StopczynskiR.E. NormolleD.P. HartmanD.J. YingH. DeBerryJ.J. BielefeldtK. RhimA.D. DePinhoR.A. AlbersK.M. DavisB.M. Neuroplastic changes occur early in the development of pancreatic ductal adenocarcinoma.Cancer Res.20147461718172710.1158/0008‑5472.CAN‑13‑2050 24448244
     [Google Scholar]
  118. TanX. SivakumarS. BednarschJ. WiltbergerG. KatherJ.N. NiehuesJ. de Vos-GeelenJ. Valkenburg-van IerselL. KintslerS. RoethA. HaoG. LangS. CoolsenM.E. den DulkM. AberleM.R. KoolenJ. GaisaN.T. Olde DaminkS.W.M. NeumannU.P. HeijL.R. Nerve fibers in the tumor microenvironment in neurotropic cancer—pancreatic cancer and cholangiocarcinoma.Oncogene202140589990810.1038/s41388‑020‑01578‑4 33288884
     [Google Scholar]
  119. ParteckeL.I. KädingA. TrungD.N. DiedrichS. SendlerM. WeissF. KühnJ.P. MayerleJ. BeyerK. von BernstorffW. HeideckeC.D. KeßlerW. Subdiaphragmatic vagotomy promotes tumor growth and reduces survival via TNFα in a murine pancreatic cancer model.Oncotarget2017814225012251210.18632/oncotarget.15019 28160574
     [Google Scholar]
  120. ParteckeL.I. SpeerforckS. KädingA. SeubertF. KühnS. LorenzE. SchwandkeS. SendlerM. KeßlerW. TrungD.N. OswaldS. WeissF.U. MayerleJ. HenkelC. MengesP. BeyerK. LerchM.M. HeideckeC.D. von BernstorffW. Chronic stress increases experimental pancreatic cancer growth, reduces survival and can be antagonised by beta-adrenergic receptor blockade.Pancreatology201616342343310.1016/j.pan.2016.03.005 27083074
     [Google Scholar]
  121. Kim-FuchsC. LeC.P. PimentelM.A. ShacklefordD. FerrariD. AngstE. HollandeF. SloanE.K. Chronic stress accelerates pancreatic cancer growth and invasion: A critical role for beta-adrenergic signaling in the pancreatic microenvironment.Brain Behav. Immun.201440404710.1016/j.bbi.2014.02.019 24650449
     [Google Scholar]
  122. ZengQ. MichaelI.P. ZhangP. SaghafiniaS. KnottG. JiaoW. McCabeB.D. GalvánJ.A. RobinsonH.P.C. ZlobecI. CirielloG. HanahanD. Synaptic proximity enables NMDAR signalling to promote brain metastasis.Nature2019573777552653110.1038/s41586‑019‑1576‑6 31534217
     [Google Scholar]
  123. LiL. ZengQ. BhutkarA. GalvánJ.A. KaramitopoulouE. NoordermeerD. GKAP acts as a genetic modulator of NMDAR signaling to govern invasive tumor growth.Cancer Cell20183373675110.1016/j.ccell.2018.02.011
     [Google Scholar]
  124. RungeT.M. AbramsJ.A. ShaheenN.J. Epidemiology of Barrett’s esophagus and esophageal adenocarcinoma.Gastroenterol. Clin. North Am.201544220323110.1016/j.gtc.2015.02.001 26021191
     [Google Scholar]
  125. MittalR. VaeziM.F. Esophageal motility disorders and gastroesophageal reflux disease.N. Engl. J. Med.2020383201961197210.1056/NEJMra2000328 33176086
     [Google Scholar]
  126. BlondyS. ChristouN. DavidV. VerdierM. JauberteauM.O. MathonnetM. PerraudA. Neurotrophins and their involvement in digestive cancers.Cell Death Dis.201910212310.1038/s41419‑019‑1385‑8 30741921
     [Google Scholar]
  127. ZhouY. SinhaS. SchwartzJ.L. AdamiG.R. A subtype of oral, laryngeal, esophageal, and lung, squamous cell carcinoma with high levels of TrkB-T1 neurotrophin receptor mRNA.BMC Cancer201919160710.1186/s12885‑019‑5789‑8 31221127
     [Google Scholar]
  128. BakstR. L. WongR. J. Mechanisms of perineural invasion.J. Neurolog Surg. Part B: Skull Base20167709610610.1055/s‑0036‑1571835
     [Google Scholar]
  129. TsunodaS. OkumuraT. ItoT. MoriY. SomaT. WatanabeG. KaganoiJ. ItamiA. SakaiY. ShimadaY. Significance of nerve growth factor overexpression and its autocrine loop in oesophageal squamous cell carcinoma.Br. J. Cancer200695332233010.1038/sj.bjc.6603255 16832412
     [Google Scholar]
  130. OkumuraT. TsunodaS. MoriY. ItoT. KikuchiK. WangT.C. YasumotoS. ShimadaY. The biological role of the low-affinity p75 neurotrophin receptor in esophageal squamous cell carcinoma.Clin. Cancer Res.200612175096510310.1158/1078‑0432.CCR‑05‑2852 16951226
     [Google Scholar]
  131. GriffinN. RoweC.W. GaoF. JoblingP. WillsV. WalkerM.M. FaulknerS. HondermarckH. Clinicopathological significance of nerves in esophageal cancer.Am. J. Pathol.202019091921193010.1016/j.ajpath.2020.05.012 32479822
     [Google Scholar]
  132. GaoA. WangL. LiJ. LiH. HanY. MaX. Prognostic value of perineural invasion in esophageal and esophagogastric junction carcinoma: A meta-analysis.Dis. mark.2016201610.1155/2016/7340180
     [Google Scholar]
  133. XuG. FengF. LiuZ. LiuS. ZhengG. XiaoS. CaiL. YangX. LiG. LianX. GuoM. SunL. YangJ. FanD. LuQ. ZhangH. Prognosis and progression of ESCC patients with perineural invasion.Sci. Rep.2017714382810.1038/srep43828 28256609
     [Google Scholar]
  134. YamadaT. AlpersD.H. KallooA.N. KaplowitzN. OwyangC. PowellD.W. Textbook of gastroenterology.John Wiley & Sons2011
     [Google Scholar]
  135. XieG. DrachenbergC. YamadaM. WessJ. RaufmanJ.P. Cholinergic agonist-induced pepsinogen secretion from murine gastric chief cells is mediated by M 1 and M 3 muscarinic receptors.Am. J. Physiol. Gastrointest. Liver Physiol.20052893G521G52910.1152/ajpgi.00105.2004 15933222
     [Google Scholar]
  136. ZhaoC-M. HayakawaY. KodamaY. MuthupalaniS. WestphalenC.B. AndersenG.T. Denervation suppresses gastric tumorigenesis.Sci. transl. med.20146250ra115250ra11510.1126/scitranslmed.3009569
     [Google Scholar]
  137. BahmanyarS. YeW. DickmanP.W. NyrénO. Long-term risk of gastric cancer by subsite in operated and unoperated patients hospitalized for peptic ulcer.Offic. J. Am. Coll. Gastroent.20071021185119110.1111/j.1572‑0241.2007.01161.x
     [Google Scholar]
  138. WangL. XuJ. XiaY. YinK. LiZ. LiB. WangW. XuH. YangL. XuZ. Muscarinic acetylcholine receptor 3 mediates vagus nerve-induced gastric cancer.Oncogenesis20187118810.1038/s41389‑018‑0099‑6 30459304
     [Google Scholar]
  139. WangL. ZhiX. ZhangQ. WeiS. LiZ. ZhouJ. JiangJ. ZhuY. YangL. XuH. XuZ. Muscarinic receptor M3 mediates cell proliferation induced by acetylcholine and contributes to apoptosis in gastric cancer.Tumour Biol.20163722105211710.1007/s13277‑015‑4011‑0 26346168
     [Google Scholar]
  140. YuH. XiaH. TangQ. XuH. WeiG. ChenY. DaiX. GongQ. BiF. Acetylcholine acts through M3 muscarinic receptor to activate the EGFR signaling and promotes gastric cancer cell proliferation.Sci. Rep.2017714080210.1038/srep40802 28102288
     [Google Scholar]
  141. HayakawaY. SakitaniK. KonishiM. AsfahaS. NiikuraR. TomitaH. RenzB.W. TailorY. MacchiniM. MiddelhoffM. JiangZ. TanakaT. DubeykovskayaZ.A. KimW. ChenX. UrbanskaA.M. NagarK. WestphalenC.B. QuanteM. LinC.S. GershonM.D. HaraA. ZhaoC.M. ChenD. WorthleyD.L. KoikeK. WangT.C. Nerve growth factor promotes gastric tumorigenesis through aberrant cholinergic signaling.Cancer Cell2017311213410.1016/j.ccell.2016.11.005 27989802
     [Google Scholar]
  142. VerkhratskyA. HoM.S. ZorecR. ParpuraV. The concept of neuroglia.Neuroglia in Neurodegenerative Diseases2019113
     [Google Scholar]
  143. SeguellaL. GulbransenB.D. Enteric glial biology, intercellular signalling and roles in gastrointestinal disease.Nat. Rev. Gastroenterol. Hepatol.202118857158710.1038/s41575‑021‑00423‑7 33731961
     [Google Scholar]
  144. FurnessJ.B. CallaghanB.P. RiveraL.R. ChoH-J. The enteric nervous system and gastrointestinal innervation: integrated local and central control. Microb. Endocrinol.20143971
     [Google Scholar]
  145. SchonkerenS.L. ThijssenM.S. VaesN. BoesmansW. MelotteV. The emerging role of nerves and glia in colorectal cancer.Cancers202113115210.3390/cancers13010152 33466373
     [Google Scholar]
  146. SundaresanS. MeiningerC.A. KangA.J. PhotenhauerA.L. HayesM.M. SahooN. Gastrin induces nuclear export and proteasome degradation of menin in enteric glial cells.Gastroenterology20171531555156710.1053/j.gastro.2017.08.038
     [Google Scholar]
  147. YuanR. BhattacharyaN. KenkelJ.A. ShenJ. DiMaioM.A. BagchiS. PrestwoodT.R. HabtezionA. EnglemanE.G. Enteric glia play a critical role in promoting the development of colorectal cancer.Front. Oncol.20201059589210.3389/fonc.2020.595892 33282743
     [Google Scholar]
  148. TârteaE-A. FlorescuC. DonoiuI. PiriciD. MihailoviciA.R. AlbuV-C. BălşeanuT.A. IancăuM. BadeaC.D. VereC.C. SfredelV. Implications of inflammation and remodeling of the enteric glial cells in colorectal adenocarcinoma.Rom. J. Morphol. Embryol.2017582473480 28730232
     [Google Scholar]
  149. PuiuI. AlbuC.V. TarteaE.A. CalboreanV. GheormanV. DinescuS.N. VasileR.C. DinescuV.C. BicaE.C. RomanescuF.M. TudorascuD.R. Relationships between glial enteric cells, beta-cell signaling and tumor proliferative activity in patients with colorectal neoplasia.Revista de Chimie201869102744274810.37358/RC.18.10.6617
     [Google Scholar]
  150. SeguellaL. RinaldiF. MarianecciC. CapuanoR. PesceM. AnnunziataG. CasanoF. BassottiG. SidoniA. MiloneM. ApreaG. de PalmaG.D. CarafaM. PesceM. EspositoG. SarnelliG. Pentamidine niosomes thwart S100B effects in human colon carcinoma biopsies favouring wt p53 rescue.J. Cell. Mol. Med.20202453053306310.1111/jcmm.14943 32022398
     [Google Scholar]
  151. RaniM. WeadgeJ.T. JabajiS. Isolation and characterization of biosurfactant-producing bacteria from oil well batteries with antimicrobial activities against food-borne and plant pathogens.Front. Microbiol.2020116410.3389/fmicb.2020.00064 32256455
     [Google Scholar]
  152. FerdoushiA. LiX. GriffinN. FaulknerS. JamaluddinM.F.B. GaoF. JiangC.C. van HeldenD.F. TanwarP.S. JoblingP. HondermarckH. Schwann cell stimulation of pancreatic cancer cells: A proteomic analysis.Front. Oncol.202010160110.3389/fonc.2020.01601 32984024
     [Google Scholar]
  153. WanC. YanX. HuB. ZhangX. Emerging roles of the nervous system in gastrointestinal cancer development.Cancers20221415372210.3390/cancers14153722 35954387
     [Google Scholar]
  154. LiuV. DietrichA. KasparekM.S. BenhaqiP. SchneiderM.R. SchemannM. SeeligerH. KreisM.E. Extrinsic intestinal denervation modulates tumor development in the small intestine of ApcMin/+ mice.J. Exp. Clin. Cancer Res.20153413910.1186/s13046‑015‑0159‑0 25925839
     [Google Scholar]
  155. SadighparvarS. DarbandS.G. Ghaderi-PakdelF. mihanfar, A.; Majidinia, M. Parasympathetic, but not sympathetic denervation, suppressed colorectal cancer progression.Eur. J. Pharmacol.202191317462610.1016/j.ejphar.2021.174626 34774852
     [Google Scholar]
  156. AmitM. Na’araS. GilZ. Mechanisms of cancer dissemination along nerves.Nat. Rev. Cancer201616639940810.1038/nrc.2016.38 27150016
     [Google Scholar]
  157. HuntP.J. KabotyanskiK.E. CalinG.A. XieT. MyersJ.N. AmitM. Interrupting neuron—tumor interactions to overcome treatment resistance.Cancers20201212374110.3390/cancers12123741 33322770
     [Google Scholar]
  158. LiangD. ShiS. XuJ. ZhangB. QinY. JiS. XuW. LiuJ. LiuL. LiuC. LongJ. NiQ. YuX. New insights into perineural invasion of pancreatic cancer: More than pain.Biochim. Biophys. Acta201618652111122 26794395
     [Google Scholar]
  159. SalomanJ.L. AlbersK.M. LiD. HartmanD.J. CrawfordH.C. MuhaE.A. RhimA.D. DavisB.M. Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer.Proc. Natl. Acad. Sci.2016113113078308310.1073/pnas.1512603113 26929329
     [Google Scholar]
  160. YeD. XuH. TangQ. XiaH. ZhangC. BiF. The role of 5-HT metabolism in cancer.Biochimica et Biophysica Acta20211876188618
     [Google Scholar]
  161. AbediniF. AmjadiO. Hedayatizadeh-OmranA. LiraS.A. AhangariG. Serotonin receptors and acetylcholinesterase gene expression alternations: The potential value on tumor microenvironment of gastric cancer.Oncology2023101741542410.1159/000530878 37231904
     [Google Scholar]
  162. LiT. FuB. ZhangX. ZhouY. YangM. CaoM. ChenY. TanY. HuR. Overproduction of gastrointestinal 5-HT promotes colitis-associated colorectal cancer progression via enhancing NLRP3 inflammasome activation.Cancer Immunol. Res.2021991008102310.1158/2326‑6066.CIR‑20‑1043 34285037
     [Google Scholar]
  163. PrenzelN. ZwickE. DaubH. LesererM. AbrahamR. WallaschC. UllrichA. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF.Nature1999402676488488810.1038/47260 10622253
     [Google Scholar]
  164. HammondW.A. SwaikaA. ModyK. Pharmacologic resistance in colorectal cancer: A review.Ther. Adv. Med. Oncol.201681578410.1177/1758834015614530 26753006
     [Google Scholar]
  165. RosenfeldG.C. Isolated parietal cells: Adrenergic response and pharmacology.J. Pharmacol. Exp. Ther.19842293763767 6202870
     [Google Scholar]
  166. AliO. TolaymatM. HuS. XieG. RaufmanJ.P. Overcoming obstacles to targeting muscarinic receptor signaling in colorectal cancer.Int. J. Mol. Sci.202122271610.3390/ijms22020716 33450835
     [Google Scholar]
  167. LiuH. HofmannJ. FishI. SchaakeB. EitelK. BartuschatA. KaindlJ. RamppH. BanerjeeA. HübnerH. ClarkM.J. VincentS.G. FisherJ.T. HeinrichM.R. HirataK. LiuX. SunaharaR.K. ShoichetB.K. KobilkaB.K. GmeinerP. Structure-guided development of selective M3 muscarinic acetylcholine receptor antagonists.Proc. Natl. Acad. Sci.201811547120461205010.1073/pnas.1813988115 30404914
     [Google Scholar]
  168. PengZ. HeathJ. DrachenbergC. RaufmanJ.P. XieG. Cholinergic muscarinic receptor activation augments murine intestinal epithelial cell proliferation and tumorigenesis.BMC Cancer201313120410.1186/1471‑2407‑13‑204 23617763
     [Google Scholar]
  169. SobczukP. ŁomiakM. Cudnoch-JędrzejewskaA. Dopamine D1 receptor in cancer.Cancers20201211323210.3390/cancers12113232 33147760
     [Google Scholar]
  170. SeoE.J. SugimotoY. GretenH.J. EfferthT. Repurposing of bromocriptine for cancer therapy.Front. Pharmacol.20189103010.3389/fphar.2018.01030 30349477
     [Google Scholar]
  171. KamazaniF.M. Sotoodehnejad nematalahi, F.; Siadat, S.D.; Pornour, M.; Sheikhpour, M. A success targeted nano delivery to lung cancer cells with multi-walled carbon nanotubes conjugated to bromocriptine.Sci. Rep.20211112441910.1038/s41598‑021‑03031‑2 34952904
     [Google Scholar]
  172. YangY. MamouniK. LiX. ChenY. KavuriS. DuY. FuH. KucukO. WuD. Repositioning dopamine D2 receptor agonist bromocriptine to enhance docetaxel chemotherapy and treat bone metastatic prostate cancer.Mol. Cancer Ther.20181791859187010.1158/1535‑7163.MCT‑17‑1176 29907594
     [Google Scholar]
  173. MancusiR. MonjeM. The neuroscience of cancer.Nature2023618796546747910.1038/s41586‑023‑05968‑y 37316719
     [Google Scholar]
  174. LiaoP. SongK. ZhuZ. LiuZ. ZhangW. LiW. HuJ. HuQ. ChenC. ChenB. McLeodH.L. PeiH. ChenL. HeY. Propranolol suppresses the growth of colorectal cancer through simultaneously activating autologous CD8+ T cells and inhibiting tumor AKT/MAPK pathway.Clin. Pharmacol. Ther.2020108360661510.1002/cpt.1894 32418204
     [Google Scholar]
  175. LvG.B. WangT.T. ZhuH.L. WangH.K. SunW. ZhaoL.F. Vortioxetine induces apoptosis and autophagy of gastric cancer AGS cells via the PI3K/AKT pathway.FEBS Open Bio202010102157216510.1002/2211‑5463.12944 32750222
     [Google Scholar]
  176. CurtisJ.J. VoN.T.K. SeymourC.B. MothersillC.E. 5-HT 2A and 5-HT 3 receptors contribute to the exacerbation of targeted and non-targeted effects of ionizing radiation-induced cell death in human colon carcinoma cells.Int. J. Radiat. Biol.202096448249010.1080/09553002.2020.1704911 31846381
     [Google Scholar]
  177. LeeH. ShimS. KongJ.S. KimM.J. ParkS. LeeS.S. KimA. Retracted: Overexpression of dopamine receptor D2 promotes colorectal cancer progression by activating the β‐catenin/ZEB1 axis.Cancer Sci.202111293732374310.1111/cas.15026 34118099
     [Google Scholar]
  178. ColeS.W. SoodA.K. Molecular pathways: Beta-adrenergic signaling in cancer.Clin. Cancer Res.20121851201120610.1158/1078‑0432.CCR‑11‑0641 22186256
     [Google Scholar]
  179. CiureaR.N. RogoveanuI. PiriciD. TârteaG.C. StrebaC.T. FlorescuC. CătălinB. PuiuI. TârteaE.A. VereC.C. B2 adrenergic receptors and morphological changes of the enteric nervous system in colorectal adenocarcinoma.World J. Gastroenterol.20172371250126110.3748/wjg.v23.i7.1250 28275305
     [Google Scholar]
  180. MusselmanR.P. BennettS. LiW. MamdaniM. GomesT. van WalravenC. BousheyR. Al-ObeedO. Al-OmranM. AuerR.C. Association between perioperative beta blocker use and cancer survival following surgical resection.Eur. J. Surg. Oncol.20184481164116910.1016/j.ejso.2018.05.012 29858097
     [Google Scholar]
  181. ShinV.Y. JinH.C. NgE.K.O. YuJ. LeungW.K. ChoC.H. SungJ.J.Y. Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine receptor (nAChR) and β-adrenergic receptor signaling pathways.Toxicol. Appl. Pharmacol.2008233225426110.1016/j.taap.2008.08.012 18805435
     [Google Scholar]
  182. KettererK. RaoS. FriessH. WeissJ. BüchlerM.W. KorcM. Reverse transcription-PCR analysis of laser-captured cells points to potential paracrine and autocrine actions of neurotrophins in pancreatic cancer.Clin. Cancer Res.200391451275136 14613990
     [Google Scholar]
  183. BanhR.S. BiancurD.E. YamamotoK. SohnA.S. WaltersB. KuljaninM. Neurons release serine to support mRNA translation in pancreatic cancer.Cell20201831202121810.1016/j.cell.2020.10.016
     [Google Scholar]
/content/journals/lddd/10.2174/0115701808258045231010102318
Loading
The Role of Neuronal Pathways in Gastrointestinal Cancers: Targets for Prevention and Treatment
Letters in Drug Design & Discovery 21, 2875 (2024); https://doi.org/10.2174/0115701808258045231010102318
/content/journals/lddd/10.2174/0115701808258045231010102318
/content/journals/lddd/10.2174/0115701808258045231010102318
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): gastrointestinal cancers; GI; humoral; Neural pathway; prevention; tumor therapy

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test