Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Protein and Peptide Letters
  4. Volume 32, Issue 3
  5. Article
Volume 32, Issue 3
  • ISSN: 0929-8665
  • E-ISSN: 1875-5305

Abstract

Background

MARVEL domain-containing 1 (MARVELD1) has been implicated in the progression of several cancers, but its role in pancreatic adenocarcinoma (PAAD) remains poorly understood.

Methods

RNA-seq data from the TCGA-PAAD and GTEx-Pancreas cohorts were analyzed to assess MARVELD1 expression. Stable MARVELD1 knockdown and overexpression were conducted in BxPC3 and PANC-1 cells. Cell viability, proliferation, migration, and invasion were evaluated using functional assays, and western blotting was employed to examine EMT-associated protein levels, including Vimentin, MMP2, MMP9, and E-cadherin. Differentially expressed genes (DEGs) between MARVELD1-high and MARVELD1-low groups were identified, and pathway enrichment analyses were performed.

Results

We observed a significant increase of MARVELD1 in PAAD patient samples, with elevated MARVELD1 levels correlating with poor clinical survival. Knockdown of MARVELD1 in PAAD cells remarkably decreased cell proliferation and colony formation, while overexpression of MARVELD1 enhanced these properties. Moreover, simulated cell invasion and migration assay further suggested that MARVELD1 might contribute to PAAD cell aggressiveness. Mechanistically, MARVELD1 promoted tumor cell migration and invasion through the activation of Vimentin, MMP2, and MMP9 protein while suppressing E-cadherin. Bioinformatics analysis revealed that MARVELD1-high samples were enriched in EMT-related pathways, including TGF-β receptor signaling, actin cytoskeleton regulation, and cell adhesion.

Conclusion

Taken together, our study highlights the roles of MARVELD1 in promoting tumor cell proliferation and invasion, suggesting its potential application as a prognostic and diagnostic biomarker for PAAD in the clinical context.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ppl/10.2174/0109298665359781250114055525
2025-01-21
2025-06-26

  • From This Site

    /content/journals/ppl/10.2174/0109298665359781250114055525
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. ChenY. YinX. XuR. RuzeR. SongJ. YinC. HuC. WangC. XuQ. ZhaoY. Cancer-associated endocrine cells participate in Pancreatic carcinogenesis.Gastroenterology2024167611671182.e2310.1053/j.gastro.2024.07.01639048054
     [Google Scholar]
  2. ChungK.M. SinghJ. LawresL. DoransK.J. GarciaC. BurkhardtD.B. RobbinsR. BhutkarA. CardoneR. ZhaoX. BabicA. VayrynenS.A. Dias CostaA. NowakJ.A. ChangD.T. DunneR.F. HezelA.F. KoongA.C. WilhelmJ.J. BellinM.D. NylanderV. GloynA.L. McCarthyM.I. KibbeyR.G. KrishnaswamyS. WolpinB.M. JacksT. FuchsC.S. MuzumdarM.D. Endocrine-exocrine signaling drives obesity-associated pancreatic ductal adenocarcinoma.Cell20201814832847.e1810.1016/j.cell.2020.03.06232304665
     [Google Scholar]
  3. ChenX. ZehH.J. KangR. KroemerG. TangD. Cell death in pancreatic cancer: From pathogenesis to therapy.Nat. Rev. Gastroenterol. Hepatol.2021181180482310.1038/s41575‑021‑00486‑634331036
     [Google Scholar]
  4. ShermanM.H. BeattyG.L. Tumor microenvironment in pancreatic cancer pathogenesis and therapeutic resistance.Annu. Rev. Pathol.202318112314810.1146/annurev‑pathmechdis‑031621‑02460036130070
     [Google Scholar]
  5. KaltsasG.A. BesserG.M. GrossmanA.B. The diagnosis and medical management of advanced neuroendocrine tumors.Endocr. Rev.200425345851110.1210/er.2003‑001415180952
     [Google Scholar]
  6. StorzP. Acinar cell plasticity and development of pancreatic ductal adenocarcinoma.Nat. Rev. Gastroenterol. Hepatol.201714529630410.1038/nrgastro.2017.1228270694
     [Google Scholar]
  7. DiMagnoE.P. Pancreatic cancer: Clinical presentation, pitfalls and early clues.Ann. Oncol.199910Suppl. 4S140S14210.1093/annonc/10.suppl_4.S14010436807
     [Google Scholar]
  8. YanX. ZhengW. XuF.S. ChangH.L. ZhangY. ZhangZ.Y. ZhangY.H. Identification and validation of a novel cuproptosis signature for stratifying different prognostic, immune, metabolic, and therapeutic landscapes in pancreatic adenocarcinoma.Eur. Rev. Med. Pharmacol. Sci.20242852024205038497885
     [Google Scholar]
  9. NeoptolemosJ.P. KleeffJ. MichlP. CostelloE. GreenhalfW. PalmerD.H. Therapeutic developments in pancreatic cancer: Current and future perspectives.Nat. Rev. Gastroenterol. Hepatol.201815633334810.1038/s41575‑018‑0005‑x29717230
     [Google Scholar]
  10. HuZ.I. O’ReillyE.M. Therapeutic developments in pancreatic cancer.Nat. Rev. Gastroenterol. Hepatol.202421172410.1038/s41575‑023‑00840‑w37798442
     [Google Scholar]
  11. MaroniL. RavaioliM. PinnaA.D. Why is pancreatic adenocarcinoma not screened for earlier?Expert Rev. Anticancer Ther.201616101003100410.1080/14737140.2016.122497227552648
     [Google Scholar]
  12. WangS. LiY. HanF. HuJ. YueL. YuY. ZhangY. HeJ. ZhengH. ShiS. FuX. WuH. Identification and characterization of MARVELD1, a novel nuclear protein that is down-regulated in multiple cancers and silenced by DNA methylation.Cancer Lett.20092821778610.1016/j.canlet.2009.03.00819364627
     [Google Scholar]
  13. WangZ.Y. ShiM. LiY. Importin-β1 plays a key role in the nucleocytoplasmic transportation process of MARVELD1.Mol. Biol.201549349149710.7868/S002689841503019226107903
     [Google Scholar]
  14. ZengF. TianY. ShiS. WuQ. LiuS. ZhengH. YueL. LiY. Identification of mouse MARVELD1 as a microtubule associated protein that inhibits cell cycle progression and migration.Mol. Cells201131326727410.1007/s10059‑011‑0037‑321347699
     [Google Scholar]
  15. ZhangC. HanF. ShiM. SunH. LiY. CiY. YaoY. DouP. AkhtarM. NieH. HeJ. LiY. MARVELD1 interacting with catalase regulates reactive oxygen species metabolism and mediates the sensitivity to chemotherapeutic drugs in epithelial tumors of the reproductive system.Mol. Carcinog.20195881410142610.1002/mc.2302431066116
     [Google Scholar]
  16. YuY. ZhangY. HuJ. ZhangH. WangS. HanF. YueL. QuY. ZhangY. LiangH. NieH. LiY. MARVELD1 inhibited cell proliferation and enhance chemosensitivity via increasing expression of p53 and p16 in hepatocellular carcinoma.Cancer Sci.2012103471672210.1111/j.1349‑7006.2012.02220.x22320884
     [Google Scholar]
  17. MaW. ShenH. LiQ. SongH. GuoY. LiF. ZhouX. GuoX. ShiJ. CuiQ. XingJ. DengJ. YuY. LiuW. ZhaoH. MARVELD1 attenuates arsenic trioxide-induced apoptosis in liver cancer cells by inhibiting reactive oxygen species production.Ann. Transl. Med.20197920010.21037/atm.2019.04.3831205918
     [Google Scholar]
  18. YaoY. ShiM. LiuS. LiY. GuoK. CiY. LiuW. LiY. MARVELD1 modulates cell surface morphology and suppresses epithelial–mesenchymal transition in non-small cell lung cancer.Mol. Carcinog.201655111714172710.1002/mc.2242126509557
     [Google Scholar]
  19. LiL. ZhangW. SunY. ZhangW. LuM. WangJ. JinY. XiQ. A clinical prognostic model of oxidative stress-related genes linked to tumor immune cell infiltration and the prognosis of ovarian cancer patients.Heliyon2024107e2844210.1016/j.heliyon.2024.e2844238560253
     [Google Scholar]
  20. SunH. LiuC. HanF. LinX. CaoL. LiuC. JiQ. CuiJ. YaoY. WangB. liaoY. NieH. ZhangY. LiY. The regulation loop of MARVELD1 interacting with PARP1 in DNA damage response maintains genome stability and promotes therapy resistance of cancer cells.Cell Death Differ.202330492293710.1038/s41418‑023‑01118‑z36750717
     [Google Scholar]
  21. ZhangJ. LiQ. SunQ. WangB. CuiY. LouC. YaoY. ZhangY. Epigenetic modifications inhibit the expression of MARVELD1 and in turn tumorigenesis by regulating the Wnt/β-catenin pathway in pan-cancer.J. Cancer202213122524210.7150/jca.6360834976185
     [Google Scholar]
  22. XiaL. JinP. TianW. LiangS. TanL. LiB. Up-regulation of MARVEL domain-containing protein 1 (MARVELD1) accelerated the malignant phenotype of glioma cancer cells via mediating JAK/STAT signaling pathway.Braz. J. Med. Biol. Res.2021547e1023610.1590/1414‑431x2020e1023634008750
     [Google Scholar]
  23. HaoQ. ZhanC. LianC. LuoS. CaoW. WangB. XieX. YeX. GuiT. VoenaC. PighiC. WangY. TianY. WangX. DaiP. CaiY. LiuX. OuyangS. SunS. HuQ. LiuJ. YeY. ZhaoJ. LuA. WangJ.Y. HuangC. SuB. MengF.L. ChiarleR. Pan-HammarströmQ. YeapL.S. DNA repair mechanisms that promote insertion-deletion events during immunoglobulin gene diversification.Sci. Immunol.2023881eade116710.1126/sciimmunol.ade116736961908
     [Google Scholar]
  24. XingY.Q. ZhuT.Z. RNA-binding motif protein RBM47 promotes invasiveness of glioblastoma through activation of epithelial-to-mesenchymal transition program.Genet. Test. Mol. Biomarkers2023271238439210.1089/gtmb.2023.036838156907
     [Google Scholar]
  25. GradaA. Otero-VinasM. Prieto-CastrilloF. ObagiZ. FalangaV. Research techniques made simple: Analysis of collective cell migration using the wound healing assay.J. Invest. Dermatol.20171372e11e1610.1016/j.jid.2016.11.02028110712
     [Google Scholar]
  26. MoroiM. OkumaM. JungS.M. Platelet adhesion to collagen-coated wells: Analysis of this complex process and a comparison with the adhesion to matrigel-coated wells.Biochim. Biophys. Acta Mol. Cell Res.1992113711910.1016/0167‑4889(92)90092‑P1390897
     [Google Scholar]
  27. BrabletzT. KalluriR. NietoM.A. WeinbergR.A. EMT in cancer.Nat. Rev. Cancer201818212813410.1038/nrc.2017.11829326430
     [Google Scholar]
  28. HugoH. AcklandM.L. BlickT. LawrenceM.G. ClementsJ.A. WilliamsE.D. ThompsonE.W. Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression.J. Cell. Physiol.2007213237438310.1002/jcp.2122317680632
     [Google Scholar]
  29. ZeisbergM. NeilsonE.G. Biomarkers for epithelial-mesenchymal transitions.J. Clin. Invest.200911961429143710.1172/JCI3618319487819
     [Google Scholar]
  30. WangS. HuJ. YaoY. ShiM. YueL. HanF. ZhangH. HeJ. LiuS. LiY. MARVELD1 regulates integrin β1-mediated cell adhesion and actin organization via inhibiting its pre-mRNA processing.Int. J. Biochem. Cell Biol.201345112679268710.1016/j.biocel.2013.09.00624055813
     [Google Scholar]
  31. ZhangK. CorsaC.A. PonikS.M. PriorJ.L. Piwnica-WormsD. EliceiriK.W. KeelyP.J. LongmoreG.D. The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis.Nat. Cell Biol.201315667768710.1038/ncb274323644467
     [Google Scholar]
  32. ThomasR. MenonV. ManiR. PruszakJ. Glycan epitope and integrin expression dynamics characterize neural crest epithelial-to-mesenchymal transition (emt) in human pluripotent stem cell differentiation.Stem Cell Rev. Rep.20221882952296510.1007/s12015‑022‑10393‑135727432
     [Google Scholar]
  33. WrightonK.H. EMT promotes contact inhibition of locomotion.Nat. Rev. Mol. Cell Biol.201516951810.1038/nrm404526265408
     [Google Scholar]
  34. WozniakJ. FloegeJ. OstendorfT. LudwigA. Key metalloproteinase-mediated pathways in the kidney.Nat. Rev. Nephrol.202117851352710.1038/s41581‑021‑00415‑533879883
     [Google Scholar]
  35. de AlmeidaL.G.N. ThodeH. EslambolchiY. ChopraS. YoungD. GillS. DevelL. DufourA. Matrix metalloproteinases: From molecular mechanisms to physiology, pathophysiology, and pharmacology.Pharmacol. Rev.202274371477010.1124/pharmrev.121.00034935738680
     [Google Scholar]
  36. MulthauptH.A.B. LeitingerB. GullbergD. CouchmanJ.R. Extracellular matrix component signaling in cancer.Adv. Drug Deliv. Rev.201697284010.1016/j.addr.2015.10.01326519775
     [Google Scholar]
  37. WendtM.K. AllingtonT.M. SchiemannW.P. Mechanisms of the epithelial-mesenchymal transition by TGF-beta.Future Oncol.2009581145116810.2217/fon.09.9019852727
     [Google Scholar]
  38. NalluriS.M. O’ConnorJ.W. GomezE.W. Cytoskeletal signaling in TGF β-induced epithelial–mesenchymal transition.Cytoskeleton2015721155756910.1002/cm.2126326543012
     [Google Scholar]
  39. Le BrasG.F. TaubenslagK.J. AndlC.D. The regulation of cell-cell adhesion during epithelial-mesenchymal transition, motility and tumor progression.Cell Adhes. Migr.20126436537310.4161/cam.2132622796940
     [Google Scholar]
  40. LamouilleS. XuJ. DerynckR. Molecular mechanisms of epithelial–mesenchymal transition.Nat. Rev. Mol. Cell Biol.201415317819610.1038/nrm375824556840
     [Google Scholar]
  41. HaoY. BakerD. ten DijkeP. TGF-β-mediated epithelial-mesenchymal transition and cancer metastasis.Int. J. Mol. Sci.20192011276710.3390/ijms2011276731195692
     [Google Scholar]
  42. ShiM. WangS. YaoY. LiY. ZhangH. HanF. NieH. SuJ. WangZ. YueL. CaoJ. LiY. Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer.Sci. Rep.201441754510.1038/srep0754525520033
     [Google Scholar]
  43. LiJ. YanH. ZhaoL. JiaW. YangH. LiuL. ZhouX. MiaoP. SunX. SongS. ZhaoX. LiuJ. HuangG. Inhibition of SREBP increases gefitinib sensitivity in non-small cell lung cancer cells.Oncotarget2016732523925240310.18632/oncotarget.1072127447558
     [Google Scholar]
/content/journals/ppl/10.2174/0109298665359781250114055525
Loading
MARVELD1 Promotes the Invasiveness in Pancreatic Adenocarcinoma through the Activation of Epithelial-to-Mesenchymal Transition
PPL 32, 224 (2025); https://doi.org/10.2174/0109298665359781250114055525
/content/journals/ppl/10.2174/0109298665359781250114055525
/content/journals/ppl/10.2174/0109298665359781250114055525
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): epithelial-to-mesenchymal transition; invasiveness; MARVELD1; pancreatic adenocarcinoma; prognostic marker; tumor cell growth

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