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2000
Volume 26, Issue 1
  • ISSN: 1389-4501
  • E-ISSN: 1873-5592

Abstract

This review provides a comprehensive overview of the recent advancements in research on ATF4 (Activating Transcription Factor 4) within the field of oncology. As a crucial transcription factor, ATF4 has garnered increasing attention for its role in cancer research. The review begins with an exploration of the regulatory mechanisms of ATF4, including its transcriptional control, post-translational modifications, and interactions with other transcription factors. It then highlights key research findings on ATF4's involvement in various aspects of tumor biology, such as cell proliferation, differentiation, apoptosis and survival, invasion and metastasis, and the tumor microenvironment. Furthermore, the review discusses the potential of targeting ATF4 as a novel therapeutic strategy for cancer treatment. It also explores how ATF4's interactions with existing anticancer drugs could inform the development of more effective therapeutic agents. By elucidating the role of ATF4 in tumor biology and its potential clinical applications, this review aims to provide new insights and strategies for cancer treatment.

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2024-09-30
2025-01-13
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References

  1. Global cancer burden growing, amidst mounting need for services.Saudi Med. J.202445332632738438207
    [Google Scholar]
  2. DizonD.S. KamalA.H. Cancer statistics 2024: All hands on deck.CA Cancer J. Clin.20247418910.3322/caac.2182438230825
    [Google Scholar]
  3. QiJ. LiM. WangL. HuY. LiuW. LongZ. ZhouZ. YinP. ZhouM. National and subnational trends in cancer burden in China, 2005–20: an analysis of national mortality surveillance data.Lancet Public Health2023812e943e95510.1016/S2468‑2667(23)00211‑638000889
    [Google Scholar]
  4. van HoogstratenL.M.C. VrielingA. van der HeijdenA.G. KogevinasM. RichtersA. KiemeneyL.A. Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice.Nat. Rev. Clin. Oncol.202320528730410.1038/s41571‑023‑00744‑336914746
    [Google Scholar]
  5. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.CA Cancer J. Clin.202171320924910.3322/caac.2166033538338
    [Google Scholar]
  6. CaoM. LiH. SunD. ChenW. Cancer burden of major cancers in China: A need for sustainable actions.Cancer Commun. (Lond.)202040520521010.1002/cac2.1202532359212
    [Google Scholar]
  7. FengR. SuQ. HuangX. BasnetT. XuX. YeW. Cancer situation in China: what does the China cancer map indicate from the first national death survey to the latest cancer registration?Cancer Commun. (Lond.)2023431758610.1002/cac2.1239336397729
    [Google Scholar]
  8. ChenW. ZhengR. BaadeP.D. ZhangS. ZengH. BrayF. JemalA. YuX.Q. HeJ. Cancer statistics in China, 2015.CA Cancer J. Clin.201666211513210.3322/caac.2133826808342
    [Google Scholar]
  9. LiuS. LiY. ZengX. WangH. YinP. WangL. LiuY. LiuJ. QiJ. RanS. YangS. ZhouM. Burden of Cardiovascular Diseases in China, 1990-2016.JAMA Cardiol.20194434235210.1001/jamacardio.2019.029530865215
    [Google Scholar]
  10. XiaC. DongX. LiH. CaoM. SunD. HeS. YangF. YanX. ZhangS. LiN. ChenW. Cancer statistics in China and United States, 2022: profiles, trends, and determinants.Chin. Med. J. (Engl.)2022135558459010.1097/CM9.000000000000210835143424
    [Google Scholar]
  11. de MartelC. GeorgesD. BrayF. FerlayJ. CliffordG.M. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis.Lancet Glob. Health202082e180e19010.1016/S2214‑109X(19)30488‑731862245
    [Google Scholar]
  12. SongM. ChanA.T. Environmental Factors, Gut Microbiota, and Colorectal Cancer Prevention.Clin. Gastroenterol. Hepatol.201917227528910.1016/j.cgh.2018.07.01230031175
    [Google Scholar]
  13. Perez-HerreroE Fernandez-MedardeA Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.Eur J Pharm Biopharm2015935279
    [Google Scholar]
  14. BaskarR. LeeK.A. YeoR. YeohK.W. Cancer and radiation therapy: current advances and future directions.Int. J. Med. Sci.20129319319910.7150/ijms.363522408567
    [Google Scholar]
  15. WeiG. WangY. YangG. WangY. JuR. Recent progress in nanomedicine for enhanced cancer chemotherapy.Theranostics202111136370639210.7150/thno.5782833995663
    [Google Scholar]
  16. AbbottM. UstoyevY. Cancer and the Immune System: The History and Background of Immunotherapy.Semin. Oncol. Nurs.201935515092310.1016/j.soncn.2019.08.00231526550
    [Google Scholar]
  17. PatelA. Benign vs Malignant Tumors.JAMA Oncol.202069148810.1001/jamaoncol.2020.259232729930
    [Google Scholar]
  18. MancusiR. MonjeM. The neuroscience of cancer.Nature2023618796546747910.1038/s41586‑023‑05968‑y37316719
    [Google Scholar]
  19. DiamandisE.P. Oncogenes and tumor suppressor genes: new biochemical tests.Crit. Rev. Clin. Lab. Sci.1992293-426930510.3109/104083692091146031489520
    [Google Scholar]
  20. WeinbergR.A. Oncogenes and tumor suppressor genes.CA Cancer J. Clin.199444316017010.3322/canjclin.44.3.1607621068
    [Google Scholar]
  21. ChandrashekarP. AhmadinejadN. WangJ. SekulicA. EganJ.B. AsmannY.W. KumarS. MaleyC. LiuL. Somatic selection distinguishes oncogenes and tumor suppressor genes.Bioinformatics20203661712171710.1093/bioinformatics/btz85132176769
    [Google Scholar]
  22. VerginadisI.I. AvgoustiH. MonslowJ. SkoufosG. ChingaF. KimK. LeliN.M. KaragounisI.V. BellB.I. VelalopoulouA. SalinasC.S. WuV.S. LiY. YeJ. ScottD.A. OstermanA.L. SenguptaA. WeljieA. HuangM. ZhangD. FanY. RadaelliE. TobiasJ.W. RambowF. KarrasP. MarineJ.C. XuX. HatzigeorgiouA.G. RyeomS. DiehlJ.A. FuchsS.Y. PuréE. KoumenisC. A stromal Integrated Stress Response activates perivascular cancer-associated fibroblasts to drive angiogenesis and tumour progression.Nat. Cell Biol.202224694095310.1038/s41556‑022‑00918‑835654839
    [Google Scholar]
  23. ChenC. ZhangZ. LiuC. WangB. LiuP. FangS. YangF. YouY. LiX. ATF4-dependent fructolysis fuels growth of glioblastoma multiforme.Nat. Commun.2022131610810.1038/s41467‑022‑33859‑936245009
    [Google Scholar]
  24. AmeriK. HarrisA.L. Activating transcription factor 4.Int. J. Biochem. Cell Biol.2008401142110.1016/j.biocel.2007.01.02017466566
    [Google Scholar]
  25. SaitoA. OchiaiK. KondoS. TsumagariK. MurakamiT. CavenerD.R. ImaizumiK. Endoplasmic reticulum stress response mediated by the PERK-eIF2(alpha)-ATF4 pathway is involved in osteoblast differentiation induced by BMP2.J. Biol. Chem.201128664809481810.1074/jbc.M110.15290021135100
    [Google Scholar]
  26. TalukderA.H. VadlamudiR. MandalM. KumarR. Heregulin induces expression, DNA binding activity, and transactivating functions of basic leucine zipper activating transcription factor 4.Cancer Res.200060227628110667576
    [Google Scholar]
  27. ChenD. FanZ. RauhM. BuchfelderM. EyupogluI.Y. SavaskanN. ATF4 promotes angiogenesis and neuronal cell death and confers ferroptosis in a xCT-dependent manner.Oncogene201736405593560810.1038/onc.2017.14628553953
    [Google Scholar]
  28. HardingH.P. NovoaI. ZhangY. ZengH. WekR. SchapiraM. RonD. Regulated translation initiation controls stress-induced gene expression in mammalian cells.Mol. Cell2000651099110810.1016/S1097‑2765(00)00108‑811106749
    [Google Scholar]
  29. SchochS. CibelliG. MaginA. SteinmüllerL. ThielG. Modular structure of cAMP response element binding protein 2 (CREB2).Neurochem. Int.200138760160810.1016/S0197‑0186(00)00127‑311290385
    [Google Scholar]
  30. LassotI. EstrabaudE. EmilianiS. BenkiraneM. BenarousR. Margottin-GoguetF. p300 modulates ATF4 stability and transcriptional activity independently of its acetyltransferase domain.J. Biol. Chem.200528050415374154510.1074/jbc.M50529420016219772
    [Google Scholar]
  31. RzymskiT. MilaniM. SingletonD.C. HarrisA.L. Role of ATF4 in regulation of autophagy and resistance to drugs and hypoxia.Cell Cycle20098233838384710.4161/cc.8.23.1008619887912
    [Google Scholar]
  32. ChenA. MuzzioI.A. MalleretG. BartschD. VerbitskyM. PavlidisP. YonanA.L. VronskayaS. GrodyM.B. CepedaI. GilliamT.C. KandelE.R. Inducible enhancement of memory storage and synaptic plasticity in transgenic mice expressing an inhibitor of ATF4 (CREB-2) and C/EBP proteins.Neuron200339465566910.1016/S0896‑6273(03)00501‑412925279
    [Google Scholar]
  33. SingletonD.C. HarrisA.L. Targeting the ATF4 pathway in cancer therapy.Expert Opin. Ther. Targets201216121189120210.1517/14728222.2012.72820723009153
    [Google Scholar]
  34. LongchampA. MirabellaT. ArduiniA. MacArthurM.R. DasA. Treviño-VillarrealJ.H. HineC. Ben-SahraI. KnudsenN.H. BraceL.E. ReynoldsJ. MejiaP. TaoM. SharmaG. WangR. CorpatauxJ.M. HaefligerJ.A. AhnK.H. LeeC.H. ManningB.D. SinclairD.A. ChenC.S. OzakiC.K. MitchellJ.R. Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H2S Production.Cell20181731117129.e1410.1016/j.cell.2018.03.00129570992
    [Google Scholar]
  35. DuRoseJ.B. TamA.B. NiwaM. Intrinsic capacities of molecular sensors of the unfolded protein response to sense alternate forms of endoplasmic reticulum stress.Mol. Biol. Cell20061773095310710.1091/mbc.e06‑01‑005516672378
    [Google Scholar]
  36. GriffithJ.W. LangC.M. Vitamin E and selenium status of guinea pigs with myocardial necrosis.Lab. Anim. Sci.19873767767793437753
    [Google Scholar]
  37. ZhaoC YuD HeZ BaoL FengL ChenL LiuZ HuX ZhangN WangT FuY. Endoplasmic reticulum stress-mediated autophagy activation is involved in cadmium-induced ferroptosis of renal tubular epithelial cells.Free Radic Biol Med.202117523624810.1016/j.freeradbiomed.2021.09.008
    [Google Scholar]
  38. WangJ. QiQ. ZhouW. FengZ. HuangB. ChenA. ZhangD. LiW. ZhangQ. JiangZ. BjerkvigR. PrestegardenL. ThorsenF. WangX. LiX. WangJ. Inhibition of glioma growth by flavokawain B is mediated through endoplasmic reticulum stress induced autophagy.Autophagy201814112007202210.1080/15548627.2018.150113330025493
    [Google Scholar]
  39. B’chirW. MaurinA.C. CarraroV. AverousJ. JousseC. MuranishiY. ParryL. StepienG. FafournouxP. BruhatA. The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression.Nucleic Acids Res.201341167683769910.1093/nar/gkt56323804767
    [Google Scholar]
  40. XiaoY XieX ChenZ YinG KongW ZhouJ Advances in the roles of ATF4 in osteoporosis.Biomed Pharmacother.202316911586410.1016/j.biopha.2023.115864
    [Google Scholar]
  41. Barrera-LopezJ.F. Cumplido-LasoG. Olivera-GomezM. Garrido-JimenezS. Diaz-ChamorroS. Mateos-QuirosC.M. BenitezD.A. CentenoF. Mulero-NavarroS. RomanA.C. Carvajal-GonzalezJ.M. Early Atf4 activity drives airway club and goblet cell differentiation.Life Sci. Alliance202473e20230228410.26508/lsa.20230228438176727
    [Google Scholar]
  42. DaiC. ChenX. LiJ. ComishP. KangR. TangD. Transcription factors in ferroptotic cell death.Cancer Gene Ther.202027964565610.1038/s41417‑020‑0170‑232123318
    [Google Scholar]
  43. HaoL. ZhongW. DongH. GuoW. SunX. ZhangW. YueR. LiT. GriffithsA. AhmadiA.R. SunZ. SongZ. ZhouZ. ATF4 activation promotes hepatic mitochondrial dysfunction by repressing NRF1–TFAM signalling in alcoholic steatohepatitis.Gut202170101933194510.1136/gutjnl‑2020‑32154833177163
    [Google Scholar]
  44. GaoR. KalathurR.K.R. Coto-LlerenaM. ErcanC. BuechelD. ShuangS. PiscuoglioS. DillM.T. CamargoF.D. ChristoforiG. TangF. YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis.EMBO Mol. Med.20211312e1435110.15252/emmm.20211435134664408
    [Google Scholar]
  45. TorrenceM.E. MacArthurM.R. HosiosA.M. ValvezanA.J. AsaraJ.M. MitchellJ.R. ManningB.D. The mTORC1- mediated activation of ATF4 promotes protein and glutathione synthesis downstream of growth signals.eLife202110e6332610.7554/eLife.6332633646118
    [Google Scholar]
  46. RösslerO.G. ThielG. Specificity of Stress-Responsive Transcription Factors Nrf2, ATF4, and AP-1.J. Cell. Biochem.2017118112714010.1002/jcb.2561927278863
    [Google Scholar]
  47. EbertS.M. RasmussenB.B. JudgeA.R. JudgeS.M. LarssonL. WekR.C. AnthonyT.G. MarcotteG.R. MillerM.J. YorekM.A. VellaA. VolpiE. SternJ.I. StrubM.D. RyanZ. TalleyJ.J. AdamsC.M. Biology of Activating Transcription Factor 4 (ATF4) and Its Role in Skeletal Muscle Atrophy.J. Nutr.2022152492693810.1093/jn/nxab44034958390
    [Google Scholar]
  48. WortelI.M.N. van der MeerL.T. KilbergM.S. van LeeuwenF.N. Surviving Stress: Modulation of ATF4-Mediated Stress Responses in Normal and Malignant Cells.Trends Endocrinol. Metab.2017281179480610.1016/j.tem.2017.07.00328797581
    [Google Scholar]
  49. KasettiR.B. PatelP.D. MaddineniP. PatilS. KiehlbauchC. MillarJ.C. SearbyC.C. RaghunathanV. SheffieldV.C. ZodeG.S. ATF4 leads to glaucoma by promoting protein synthesis and ER client protein load.Nat. Commun.2020111559410.1038/s41467‑020‑19352‑133154371
    [Google Scholar]
  50. RyanD.G. YangM. PragH.A. BlancoG.R. NikitopoulouE. Segarra-MondejarM. PowellC.A. YoungT. BurgerN. MiljkovicJ.L. MinczukM. MurphyM.P. von KriegsheimA. FrezzaC. Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism.eLife202110e7259310.7554/eLife.7259334939929
    [Google Scholar]
  51. HanS. ZhuL. ZhuY. MengY. LiJ. SongP. YousafzaiN.A. FengL. ChenM. WangY. JinH. WangX. Targeting ATF4-dependent pro-survival autophagy to synergize glutaminolysis inhibition.Theranostics202111178464847910.7150/thno.6002834373753
    [Google Scholar]
  52. HeF. ZhangP. LiuJ. WangR. KaufmanR.J. YadenB.C. KarinM. ATF4 suppresses hepatocarcinogenesis by inducing SLC7A11 (xCT) to block stress-related ferroptosis.J. Hepatol.202379236237710.1016/j.jhep.2023.03.01636996941
    [Google Scholar]
  53. FanC.F. MiaoY. LinX.Y. ZhangD. WangE.H. Expression of a phosphorylated form of ATF4 in lung and non-small cell lung cancer tissues.Tumour Biol.201435176577110.1007/s13277‑013‑1104‑523975372
    [Google Scholar]
  54. SunY. GongC. NiZ. HuD. NgW. ZhuX. WangL. SiG. YanX. ZhaoC. YaoC. ZhuS. Tanshinone IIA enhances susceptibility of non-small cell lung cancer cells to NK cell-mediated lysis by up-regulating ULBP1 and DR5.J. Leukoc. Biol.2021110231532510.1002/JLB.5MA1120‑776RR33909909
    [Google Scholar]
  55. ZhaoN. WangC. GuoP. HouJ. YangH. LanT. ZhouY. LiJ. BhawalU.K. LiuY. CCDC106 promotes the proliferation and invasion of ovarian cancer cells by suppressing p21 transcription through a p53-independent pathway.Bioengineered2022134109571097310.1080/21655979.2022.206675935484984
    [Google Scholar]
  56. MujcicH. RzymskiT. RouschopK.M.A. KoritzinskyM. MilaniM. HarrisA.L. WoutersB.G. Hypoxic activation of the unfolded protein response (UPR) induces expression of the metastasis-associated gene LAMP3.Radiother. Oncol.200992345045910.1016/j.radonc.2009.08.01719726095
    [Google Scholar]
  57. Bagheri-YarmandR. WilliamsM.D. Grubbse.g. GagelR.F. ATF4 Targets RET for Degradation and Is a Candidate Tumor Suppressor Gene in Medullary Thyroid Cancer.J. Clin. Endocrinol. Metab.2017102393394127935748
    [Google Scholar]
  58. Bagheri-YarmandR. SinhaK.M. GururajA.E. AhmedZ. RizviY.Q. HuangS.C. LadburyJ.E. BoglerO. WilliamsM.D. CoteG.J. GagelR.F. A novel dual kinase function of the RET proto-oncogene negatively regulates activating transcription factor 4-mediated apoptosis.J. Biol. Chem.201529018117491176110.1074/jbc.M114.61983325795775
    [Google Scholar]
  59. RozpedekW. PytelD. MuchaB. LeszczynskaH. DiehlJ.A. MajsterekI. The Role of the PERK/eIF2α/ATF4/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress.Curr. Mol. Med.201616653354410.2174/156652401666616052314393727211800
    [Google Scholar]
  60. XinY WuW QuJ WangX LeiS YuanL LiuX. Inhibition of Mitofusin-2 Promotes Cardiac Fibroblast Activation via the PERK/ATF4 Pathway and Reactive Oxygen Species.Oxid Med Cell Longev201920193649808
    [Google Scholar]
  61. YoshizawaT. HinoiE. JungD.Y. KajimuraD. FerronM. SeoJ. GraffJ.M. KimJ.K. KarsentyG. The transcription factor ATF4 regulates glucose metabolism in mice through its expression in osteoblasts.J. Clin. Invest.200911992807281710.1172/JCI3936619726872
    [Google Scholar]
  62. Gomez-SamanoMA Grajales-GomezM Zuarth-VazquezJM Navarro-FloresMF Martinez-SaavedraM Juarez-LeonOA Morales-GarciaMG Enriquez-EstradaVM Gomez-PerezFJ Cuevas-RamosD Fibroblast growth factor 21 and its novel association with oxidative stress.Redox Biol.20171133534110.1016/j.redox.2016.12.024
    [Google Scholar]
  63. GibsonJ.S. ClaassenD.O. State-of-the-art pharmacological approaches to reduce chorea in Huntington’s disease.Expert Opin. Pharmacother.20212281015102410.1080/14656566.2021.187666633550875
    [Google Scholar]
  64. Bagheri-YarmandR. SinhaK.M. LiL. LuY. CoteG.J. ShermanS.I. GagelR.F. Combinations of Tyrosine Kinase Inhibitor and ERAD Inhibitor Promote Oxidative Stress–Induced Apoptosis through ATF4 and KLF9 in Medullary Thyroid Cancer.Mol. Cancer Res.201917375176010.1158/1541‑7786.MCR‑18‑035430552230
    [Google Scholar]
  65. ZhaoY. YuY. LiH. ZhangZ. GuoS. ZhuS. GuoQ. LiP. MinL. ZhangS. FAM175B promotes apoptosis by inhibiting ATF4 ubiquitination in esophageal squamous cell carcinoma.Mol. Oncol.20191351150116510.1002/1878‑0261.1247430854784
    [Google Scholar]
  66. RecouvreuxM.V. MoldenhauerM.R. GalenkampK.M.O. JungM. JamesB. ZhangY. LowyA. BagchiA. CommissoC. Glutamine depletion regulates Slug to promote EMT and metastasis in pancreatic cancer.J. Exp. Med.20202179e2020038810.1084/jem.2020038832510550
    [Google Scholar]
  67. LiS HeY ChenK SunJ ZhangL HeY YuH LiQ. RSL3 Drives Ferroptosis through NF-kappaB Pathway Activation and GPX4 Depletion in Glioblastoma.Oxid Med Cell Longev202120212915019
    [Google Scholar]
  68. KrallA.S. MullenP.J. SurjonoF. MomcilovicM. SchmidE.W. HalbrookC.J. ThambunditA. MittelmanS.D. LyssiotisC.A. ShackelfordD.B. KnottS.R.V. ChristofkH.R. Asparagine couples mitochondrial respiration to ATF4 activity and tumor growth.Cell Metab.202133510131026.e610.1016/j.cmet.2021.02.00133609439
    [Google Scholar]
  69. TameireF. VerginadisI.I. LeliN.M. PolteC. ConnC.S. OjhaR. Salas SalinasC. ChingaF. MonroyA.M. FuW. WangP. KossenkovA. YeJ. AmaravadiR.K. IgnatovaZ. FuchsS.Y. DiehlJ.A. RuggeroD. KoumenisC. ATF4 couples MYC-dependent translational activity to bioenergetic demands during tumour progression.Nat. Cell Biol.201921788989910.1038/s41556‑019‑0347‑931263264
    [Google Scholar]
  70. WilliamsR.T. GuarecucoR. GatesL.A. BarrowsD. PassarelliM.C. CareyB. BaudrierL. JeewajeeS. LaK. PrizerB. MalikS. Garcia-BermudezJ. ZhuX.G. CantorJ. MolinaH. CarrollT. RoederR.G. Abdel-WahabO. AllisC.D. BirsoyK. ZBTB1 Regulates Asparagine Synthesis and Leukemia Cell Response to L-Asparaginase.Cell Metab.2020314852861.e610.1016/j.cmet.2020.03.00832268116
    [Google Scholar]
  71. AstT. MeiselJ.D. PatraS. WangH. GrangeR.M.H. KimS.H. CalvoS.E. OreficeL.L. NagashimaF. IchinoseF. ZapolW.M. RuvkunG. BarondeauD.P. MoothaV.K. Hypoxia Rescues Frataxin Loss by Restoring Iron Sulfur Cluster Biogenesis.Cell2019177615071521.e1610.1016/j.cell.2019.03.04531031004
    [Google Scholar]
  72. ZhouP. QuH. ShiK. ChenX. ZhuangZ. WangN. ZhangQ. LiuZ. WangL. DengK. ZhaoY. ShanT. FanG. ChenY. XiaJ. ATF4-mediated circTDRD3 promotes gastric cancer cell proliferation and metastasis by regulating the miR-891b/ITGA2 axis and AKT signaling pathway.Gastric Cancer202326456557910.1007/s10120‑023‑01392‑337062785
    [Google Scholar]
  73. DaiH. ShenK. YangY. SuX. LuoY. JiangY. ShuaiL. ZhengP. ChenZ. BieP. PUM1 knockdown prevents tumor progression by activating the PERK/eIF2/ATF4 signaling pathway in pancreatic adenocarcinoma cells.Cell Death Dis.201910859510.1038/s41419‑019‑1839‑z31395860
    [Google Scholar]
  74. MiL LiuJ ZhangY SuA TangM XingZ HeT WeiT LiZ WuW. The EPRS-ATF4-COLI pathway axis is a potential target for anaplastic thyroid carcinoma therapy. Phytomedicine2024129155670
    [Google Scholar]
  75. Clavería-CabelloA. HerranzJ.M. LatasaM.U. ArechederraM. UriarteI. Pineda-LucenaA. ProsperF. BerraondoP. AlonsoC. SangroB. García MarinJ.J. Martinez-ChantarM.L. CiordiaS. CorralesF.J. FrancalanciP. AlaggioR. Zucman-RossiJ. IndersieE. CairoS. Domingo-SàbatM. ZanattoL. Sancho-BruP. ArmengolC. BerasainC. Fernandez-BarrenaM.G. AvilaM.A. Identification and experimental validation of druggable epigenetic targets in hepatoblastoma.J. Hepatol.2023794989100510.1016/j.jhep.2023.05.03137302584
    [Google Scholar]
  76. WatanabeY. SasakiT. MiyoshiS. ShimizuM. YamauchiY. SatoR. Insulin-induced genes INSIG1 and INSIG2 mediate oxysterol-dependent activation of the PERK–eIF2α–ATF4 axis.J. Biol. Chem.2021297210098910.1016/j.jbc.2021.10098934298014
    [Google Scholar]
  77. ChoS.H. OhB. KimH.A. ParkJ.H. LeeM. Post-translational regulation of gene expression using the ATF4 oxygen-dependent degradation domain for hypoxia-specific gene therapy.J. Drug Target.201321983083610.3109/1061186X.2013.82907323952904
    [Google Scholar]
  78. HuangT. XuT. WangY. ZhouY. YuD. WangZ. HeL. ChenZ. ZhangY. DavidsonD. DaiY. HangC. LiuX. YanC. Cannabidiol inhibits human glioma by induction of lethal mitophagy through activating TRPV4.Autophagy202117113592360610.1080/15548627.2021.188520333629929
    [Google Scholar]
  79. JangS.K. HongS.E. LeeD.H. KimJ.Y. KimJ.Y. HongJ. ParkI.C. JinH.O. Inhibition of AKT Enhances the Sensitivity of NSCLC Cells to Metformin.Anticancer Res.20214173481348710.21873/anticanres.1513534230143
    [Google Scholar]
  80. LiX. ZhengJ. ChenS. MengF. NingJ. SunS. Oleandrin, a cardiac glycoside, induces immunogenic cell death via the PERK/elF2α/ATF4/CHOP pathway in breast cancer.Cell Death Dis.202112431410.1038/s41419‑021‑03605‑y33762577
    [Google Scholar]
  81. TangX GuoY ZhangS WangX TengY JinQ JinQ ShenW WangR. Solanine represses gastric cancer growth by mediating autophagy through AAMDC/MYC/ATF4/Sesn2 signaling pathway.Drug Des Devel Ther202317389402
    [Google Scholar]
  82. KangL. WangD. ShenT. LiuX. DaiB. ZhouD. ShenH. GongJ. LiG. HuY. WangP. MiX. ZhangY. TanX. PDIA4 confers resistance to ferroptosis via induction of ATF4/SLC7A11 in renal cell carcinoma.Cell Death Dis.202314319310.1038/s41419‑023‑05719‑x36906674
    [Google Scholar]
  83. WangM LuY WangH WuY XuX LiY. High ATF4 expression is associated with poor prognosis, amino acid metabolism, and autophagy in gastric cancer.Front Oncol202111740120
    [Google Scholar]
  84. MaS. WangH. LiW. YanZ. LuoX. LuP. The correlation between the expression of ATF4 and procalcitonin combined with the detection of RET mutation and the pathological stage and clinical prognosis of medullary thyroid carcinoma.Can. J. Physiol. Pharmacol.20221001192510.1139/cjpp‑2021‑031634822305
    [Google Scholar]
  85. WeiL. LinQ. LuY. LiG. HuangL. FuZ. ChenR. ZhouQ. Cancer-associated fibroblasts-mediated ATF4 expression promotes malignancy and gemcitabine resistance in pancreatic cancer via the TGF-β1/SMAD2/3 pathway and ABCC1 transactivation.Cell Death Dis.202112433410.1038/s41419‑021‑03574‑233782384
    [Google Scholar]
  86. LewerenzJ. SatoH. AlbrechtP. HenkeN. NoackR. MethnerA. MaherP. Mutation of ATF4 mediates resistance of neuronal cell lines against oxidative stress by inducing xCT expression.Cell Death Differ.201219584785810.1038/cdd.2011.16522095285
    [Google Scholar]
  87. GaoF. LiangT. LuY.W. PuL. FuX. DongX. HongT. ZhangF. LiuN. ZhouY. WangH. LiangP. GuoY. YuH. ZhuW. HuX. ChenH. ZhouB. PuW.T. MablyJ.D. WangJ. WangD.Z. ChenJ. Reduced Mitochondrial Protein Translation Promotes Cardiomyocyte Proliferation and Heart Regeneration.Circulation2023148231887190610.1161/CIRCULATIONAHA.122.06119237905452
    [Google Scholar]
  88. SawaR. OhnishiA. OhnoM. NagataM. WakeI. OkimuraY. Specific amino acids regulate Sestrin2 mRNA and protein levels in an ATF4-dependent manner in C2C12 myocytes.Biochim. Biophys. Acta, Gen. Subj.20221866913017410.1016/j.bbagen.2022.13017435597502
    [Google Scholar]
  89. TanY. ZhuJ. HashimotoK. Autophagy-related gene model as a novel risk factor for schizophrenia.Transl. Psychiatry20241419410.1038/s41398‑024‑02767‑538351068
    [Google Scholar]
  90. FurmanikM. van GorpR. WhiteheadM. AhmadS. BordoloiJ. KapustinA. SchurgersL.J. ShanahanC.M. Endoplasmic Reticulum Stress Mediates Vascular Smooth Muscle Cell Calcification via Increased Release of Grp78 (Glucose-Regulated Protein, 78 kDa)-Loaded Extracellular Vesicles.Arterioscler. Thromb. Vasc. Biol.202141289891410.1161/ATVBAHA.120.31550633297752
    [Google Scholar]
  91. WangL. ZhaoW. XiaC. LiZ. ZhaoW. XuK. WangN. LianH. RosasI.O. YuG. TRIB3 Mediates Fibroblast Activation and Fibrosis though Interaction with ATF4 in IPF.Int. J. Mol. Sci.202223241570510.3390/ijms23241570536555349
    [Google Scholar]
  92. FelsD.R. KoumenisC. The PERK/eIF2α/ATF4 module of the UPR in hypoxia resistance and tumor growth.Cancer Biol. Ther.20065772372810.4161/cbt.5.7.296716861899
    [Google Scholar]
  93. LiuQ TangQ JingX ZhangJ XiaY YanJ XuY LiJ LiY HeJ MoL Mesencephalic astrocyte-derived neurotrophic factor protects against paracetamol -induced liver injury by inhibiting PERK-ATF4-CHOP signaling pathway.Biochem Biophys Res Commun20226021639
    [Google Scholar]
  94. HaoY SamuelsY LiQ KrokowskiD GuanBJ WangC JinZ DongB CaoB FengX XiangM XuC FinkS MeropolNJ XuY ConlonRA MarkowitzS KinzlerKW VelculescuVE BrunengraberH WillisJE LaframboiseT HatzoglouM ZhangGF VogelsteinB WangZ Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer.Nat Commun201671197110.1038/ncomms11971
    [Google Scholar]
  95. WekR.C. AnthonyT.G. StaschkeK.A. Surviving and Adapting to Stress: Translational Control and the Integrated Stress Response.Antioxid. Redox Signal.2023394-635137310.1089/ars.2022.012336943285
    [Google Scholar]
  96. GuoQ. XuZ. ZhouD. FuT. WangW. SunW. XiaoL. LiuL. DingC. YinY. ZhouZ. SunZ. ZhuY. ZhouW. JiaY. XueJ. ChenY. ChenX.W. PiaoH.L. LuB. GanZ. Mitochondrial proteostasis stress in muscle drives a long-range protective response to alleviate dietary obesity independently of ATF4.Sci. Adv.2022830eabo034010.1126/sciadv.abo034035895846
    [Google Scholar]
  97. QuirósP.M. PradoM.A. ZamboniN. D’AmicoD. WilliamsR.W. FinleyD. GygiS.P. AuwerxJ. Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals.J. Cell Biol.201721672027204510.1083/jcb.20170205828566324
    [Google Scholar]
  98. BaniulyteG. DurhamS.A. MerchantL.E. SammonsM.A. Shared Gene Targets of the ATF4 and p53 Transcriptional Networks.Mol. Cell. Biol.202343842644910.1080/10985549.2023.222922537533313
    [Google Scholar]
  99. ZengH. ZhangJ. DuY. WangJ. RenY. LiM. LiH. CaiZ. ChuQ. YangC. Crosstalk between ATF4 and MTA1/HDAC1 promotes osteosarcoma progression.Oncotarget2016767329734210.18632/oncotarget.694026797758
    [Google Scholar]
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  • Article Type:
    Review Article
Keyword(s): ATF4; ER stress; malignant; targeted therapy; transcription factor; tumor
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