Deregulation of E-Cadherin in Precancerous Lesions and Gastric Cancer
Gastric cancer remains the second major cause of cancer-related deaths in the world. China and Hong Kong are among the high incidence areas in the world, showing no trend of reduction in gastric cancer incidence over the past 10 years and no improvement in the survival rate. Helicobacter pylori infection is an important etiologic risk factor in gastric cancer, and has been classified as a class I carcinogen by the World Health Organization. However, only a minority of the infected population eventually develop gastric cancer. Molecular studies of the host may give definite proof of the etiologic role of H. pylori in inducing gastric carcinoma.
E-cadherin is a transmembrane glycoprotein expressed on epithelial cells, and is responsible for homotypic cell adhesion. Defective cell adhesion may contribute to loss of contact inhibition of growth, which is an early step in carcinogenesis. The critical role of E-cadherin is underlined by the observation that familial gastric...
KeywordsGastric Cancer Adenomatous Polyposis Coli Intestinal Metaplasia Bullous Pemphigoid Diffuse Gastric Cancer
- Behrens J, Vakaet L, Friis R, Winterhager E, Van Roy F, Mareel MM, Birchmeier W. Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene. J Cell Biol 1993; 120: 757–766.CrossRefPubMedGoogle Scholar
- Guilford PJ, Hopkins JBW, Grady WM, Markowitz SD, Willis J, Lynch H, Rajput A, Wiesner GL, Lindor NM, Burgart LJ, Toro TT, Lee D, Limacher JM, Shaw DW, Findlay MPN, Reeve AE. E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer. Hum Mutat 1999; 14: 249–255.CrossRefPubMedGoogle Scholar
- Humar B, Toro T, Graziano F, Muller H, Dobbie Z, Kwang-Yang H, Eng C, Hampel H, Gilbert D, Winship I, Parry S, Ward R, Findlay M, Christian A, Tucker M, Tucker K, Merriman T, Guilford P. Novel germline CDH1 mutations in hereditary diffuse gastric cancer families. Hum Mutat 2002; 19: 518–525.CrossRefPubMedGoogle Scholar
- Oliveira C, Bordin MC, Grehan N, Huntsman D, Suriano G, Machado JC, Kiviluoto T, Aaltonen L, Jackson CE, Seruca R, Caldas C. Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred. Hum Mutat 2002; 19: 510–517.CrossRefPubMedGoogle Scholar
- Tamura G, Yin J, Wang S, Fleisher AS, Zou T, Abraham JM, Kong D, Smolinski KN, Wilson KT, James SP, Silverberg SG, Nishizuka S, Terashima M, Motoyama T, Meltzer SJ. E-Cadherin gene promoter hypermethylation in primary human gastric carcinomas. J Natl Cancer Inst 2000; 92: 569–573.CrossRefPubMedGoogle Scholar