Epithelial-mesenchymal transition in gastric cancer (Review)

  • Authors:
    • Masaru Katoh
  • View Affiliations

  • Published online on: December 1, 2005     https://doi.org/10.3892/ijo.27.6.1677
  • Pages: 1677-1683
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), surgical gastrectomy, and chemotherapy are therapeutic options of gastric cancer; how-ever, prognosis of advanced gastric cancer patients is still poor. Gastric cancer cells with fibroblastoid morphological changes show increased motility and invasiveness due to decreased cell-cell adhesion, which are reminiscent of epithelial-mesenchymal transition (EMT) during embryonic development. Here, EMT signaling networks in gastric cancer were reviewed. E-cadherin at adherens junction is a key molecular target of EMT. CDH1 gene at human chromosome 16q22.1 encodes E-cadherin. Familial diffuse type gastric cancer occurs due to germ-line mutations of the CDH1 gene. Down-regulation of E-cadherin function due to mutation, deletion, CpG hyper-methylation, and SNAIL (SNAI1)- or SIP1-mediated transcriptional repression of the CDH1 gene leads to EMT in gastric cancer. Amplification of ERBB2, MET, FGFR2, PIK3CA, AKT1 genes, up-regulation of WNT2, WNT2B, WNT8B, and down-regulation of SFRP1 lead to EMT in gastric cancer through GSK3β inhibition and following SNAIL-mediated CDH1 repression. Claudin (CLDN) and PAR3/PAR6/aPKC complex at tight junction are other key molecular targets of EMT. CLDN23 gene is down-regulated in intestinal type gastric cancer. Down-regulation of PAR3/PAR6/aPKC complex also leads to EMT. Single nucleotide polymorphisms (SNPs) and copy number polymorphisms (CNPs) of genes encoding EMT signaling molecules will be identified as novel risk factors of gastric cancer. In addition, antibodies, RNAi compounds, and small molecular inhibitors for EMT signaling molecules will be developed as novel therapeutic agents for gastric cancer. Personalized medicine based on the combination of genetic screening and novel therapeutic agents could dramatically improve the prognosis of gastric cancer patients in the future.

Related Articles

Journal Cover

December 2005
Volume 27 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Katoh M: Epithelial-mesenchymal transition in gastric cancer (Review). Int J Oncol 27: 1677-1683, 2005
APA
Katoh, M. (2005). Epithelial-mesenchymal transition in gastric cancer (Review). International Journal of Oncology, 27, 1677-1683. https://doi.org/10.3892/ijo.27.6.1677
MLA
Katoh, M."Epithelial-mesenchymal transition in gastric cancer (Review)". International Journal of Oncology 27.6 (2005): 1677-1683.
Chicago
Katoh, M."Epithelial-mesenchymal transition in gastric cancer (Review)". International Journal of Oncology 27, no. 6 (2005): 1677-1683. https://doi.org/10.3892/ijo.27.6.1677