Epithelial polarity attenuates gastric cancer/therapeutic interventions

Review Article
Journal of Cellular Cancer  Volume 6, Issue 1, pages 1-13
Published: June 04, 2014

Elisabeth S. Gillespie,Timothy H. Rong, Kevin Phesse, Elena Fetler, Kyung Soon Wang


Gastric adenocarcinoma is the second leading cause of cancer-related death in the world. Epithelial cells form intercellular adhesions, characteristically exhibit apicobasal polarity, and orient their mitotic spindles in the plane of the epithelial sheet. Defects in these attributes result in the tissue disorganization associated with cance and resulting in loss of epithelial polarity, which often correlates in extent with the aggressiveness of the tumor. We review how the polarity strategies integrates and used by gastric cancer and role in therapy, this needs to understanding more mechanistic of gastric cancers which should result in better targets for gastric cancer therapy.

Keywords: Gastric cancer; Polarity; Intercellular adhesions; Mitosis; Cancer

Purchase access to this articleReferencesExport Citation
Purchase this article at rate $55.00 and received Full-Text/PDF You will have online immediate access to article following the completion of this purchase and you may download and print a copy of each article for your personal use. Purchase Article


  1. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420(6917):860-7. [PubMed]
  2. Moss SF, Blaser MJ. Mechanisms of disease: Inflammation and the origins of cancer. Nat Clin Pract Oncol 2005; 2(2):90-7. [PubMed]
  3. Tanos B, Rodriguez-Boulan E. The epithelial polarity program: machineries involved and their hijacking by cancer. Oncogene 2008;27:6939–6957. [Abstract/Full-Text]
  4. Fuchs E, Tumbar T, Guasch G. Socializing with the neighbors: stem cells and their niche. Cell 2004;116(6):769–778. [PubMed]
  5. Perez-Moreno M, Fuchs E. Catenins: keeping cells from getting their signals crossed. Developmental Cell 2006;11(5):601–612. [PMC free article] [PubMed]
  6. Sakakibara A, Furuse M, Saitou M, Ando-Akatsuka Y, Tsukita S. Possible involvement of phosphorylation of occludin in tight junction formation. The Journal of Cell Biology 1997;137(6):1393–1401. [PubMed]
  7. Andreeva AY, Krause E, Müller EC, et al. Protein kinase C regulates the phosphorylation and cellular localization of occludin. The Journal of Biological Chemistry. 2001;276(42):38480–38486. [PubMed]
  8. Ikenouchi J, Furuse M, Furuse K, et al. Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. The Journal of Cell Biology 2005;171(6):939–945. [PMC free article] [PubMed]
  9. Matter K, Balda MS. Epithelial tight junctions, gene expression and nucleo-junctional interplay. Journal of Cell Science. 2007;120(9):1505–1511. [PubMed]
  10. Asakura T, Nakanishi H, Sakisaka T, et al. Similar and differential behaviour between the nectin-afadin-ponsin and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells. Genes Cells. 1999;4(10):573–581. [PubMed]
  11. Bazzoni G, Martínez-Estrada OM, Orsenigo F, et al. Interaction of junctional adhesion molecule with the tight junction components ZO-1, cingulin, and occludin. The Journal of Biological Chemistry 2000;275(27):20520–20526. [PubMed]
  12. Nishimura M, Kakizaki M, Ono Y, et al. JEAP, a novel component of tight junctions in exocrine cells. The Journal of Biological Chemistry 2002;277(7):5583–5587. [PubMed]
  13. Yousif NG, Al-Amran FG. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin) induced cardiac injury in mice. BMC Cardiovasc Disord 2011;11:62. [PubMed]
  14. Furuse M, Sasaki H, Fujimoto K, et al. A single gene product, claudin-1 or -2, reconstitutes tight junction strands and recruits occludin in fibroblasts. Journal of Cell Biology 1998;143(2):391–401. [PMC free article] [PubMed]
  15. Han J, Dong RG, Harris MJ. Potential effects of TPX2 in clinicopathologic features, prognosis and metastasis of gastric cancer patients. American Journal of BioMedicine 2014; 2(1):124–131. [Abstract/Full-Text]
  16. Umeda K, Ikenouchi J, Katahira-Tayama S, et al. ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell 2006;126(4):741–754. [PubMed]
  17. Mostov KE, Verges M, Altschuler Y. Membrane traffic in polarized epithelial cells. Current Opinion in Cell Biology 2000;12(4):483–490. [PubMed]
  18. Schneeberger EE, Lynch RD. The tight junction: a multifunctional complex. American Journal of Physiology 2004;286(6):C1213–C1228. [PubMed]
  19. González-Mariscal L, Nava P, Hernández S. Critical role of tight junctions in drug delivery across epithelial and endothelial cell layers. Journal of Membrane Biology 2005;207(2):55–68. [PubMed]
  20. Yousif NG, Al-Amran FG, Hadi N, Lee J, Adrienne J. Expression of IL-32 modulates NF-κB and p38 MAP kinase pathways in human esophageal cancer. Cytokine 2013;61(1):223-7. [PubMed]
  21. Zhang JJ, Wang YL, Feng XB, Song XD, Liu WB. Rosmarinic acid inhibits proliferation and induces apoptosis of hepatic stellate cells. Biol Pharm Bull. 2011;34(3):343–348. [PubMed]
  22. Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell. 2009;139(4):693–706. [PMC free article] [PubMed]
  23. Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond. Cell. 2008;134(5):703–707.
  24. Madhok BM, Yeluri S, Perry SL, Hughes TA, Jayne DG. Targeting glucose metabolism: an emerging concept for anticancer therapy. Am J Clin Oncol. 2011;34(6):628–635. [PubMed]
  25. Gordo J, Maximo P, Cabrita E, et al. Thymus mastichina: chemical constituents and their anti-cancer activity. Nat Prod Commun. 2012;7(1):1491–1494. [PubMed]
  26. Rosen DG, Mercado-Uribe I, Yang G, et al. The role of constitutively active signal transducer and activator of transcription 3 in ovarian tumorigenesis and prognosis. Cancer. 2006;107(11):2730–2740. [PubMed]
  27. Wang J, Yang S, Zhang H, et al. Aurora-A as an independent molecular prognostic marker in gastric cancer. OncolRep 2011;26(1):23–32.
  28. Hohenberger P, Gretschel S. Gastric cancer. Lancet. 2003;362(9380):305–315. [PubMed]
  29. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20. [PubMed]
  30. Bolanos-Garcia VM. Aurora kinases. Int J Biochem Cell Biol. 2005;37(8):1572–1577. [PubMed]
  31. Barr AR, Gergely F. Aurora-A: the maker and breaker of spindle poles. J Cell Sci 2007;120(Pt 17):2987–2996. [PubMed]
  32. Huck JJ, Zhang M, McDonald A, et al. MLN8054, an inhibitor of Aurora A kinase, induces senescence in human tumor cells both in vitro and in vivo. Mol Cancer Res 2010;8(3):373–384. [PubMed]
  33. Görgün G, Calabrese E, Hideshima T, et al. A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma. Blood 2010;115(25):5202–5213. [PubMed]

Journal of cellular cancer picture







Elisabeth S. Gillespie,Timothy H. Rong, Kevin Phesse, Elena Fetler, Kyung Soon Wang. Epithelial polarity attenuates gastric cancer/therapeutic interventions. Journal of Cellular Cancer 2014; 6(1):1-13.