Loss of E-Cadherin-Dependent Cell–Cell Adhesion and the Development and Progression of Cancer
Open Access
- 15 May 2017
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Cold Spring Harbor Perspectives in Biology
- Vol. 10 (3), a029330
- https://doi.org/10.1101/cshperspect.a029330
Abstract
Classical cadherins are the key molecules that control cell–cell adhesion. Notwithstanding this function, it is also clear that classical cadherins are more than just the “glue” that keeps the cells together. Cadherins are essential regulators of tissue homeostasis that govern multiple facets of cellular function and development, by transducing adhesive signals to a complex network of signaling effectors and transcriptional programs. In cancer, cadherins are often inactivated or functionally inhibited, resulting in disease development and/or progression. This review focuses on E-cadherin and its causal role in the development and progression of breast and gastric cancer. We provide a summary of the biochemical consequences and consider the conceptual impact of early (mutational) E-cadherin loss in cancer. We advocate that carcinomas driven by E-cadherin loss should be considered “actin-diseases,” caused by the specific disruption of the E-cadherin-actin connection and a subsequent dependence on sustained actomyosin contraction for tumor progression. Based on the available data from mouse and human studies we discuss opportunities for targeted clinical intervention.This publication has 166 references indexed in Scilit:
- Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancerCellular Oncology, 2013
- LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic markerNature Medicine, 2012
- The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancersNature, 2012
- Deciphering the rules of programmed cell death to improve therapy of cancer and other diseasesThe EMBO Journal, 2011
- Deletion of p120-Catenin Results in a Tumor Microenvironment with Inflammation and Cancer that Establishes It as a Tumor Suppressor GeneCancer Cell, 2011
- Coordinated protein sorting, targeting and distribution in polarized cellsNature Reviews Molecular Cell Biology, 2008
- Somatic loss of BRCA1 and p53 in mice induces mammary tumors with features of human BRCA1 -mutated basal-like breast cancerProceedings of the National Academy of Sciences of the United States of America, 2007
- Founder and Recurrent CDH1 Mutations in Families With Hereditary Diffuse Gastric CancerJAMA, 2007
- Functional role and oncogene-regulated expression of the BH3-only factor Bmf in mammary epithelial anoikis and morphogenesisProceedings of the National Academy of Sciences of the United States of America, 2007
- BIM Regulates Apoptosis during Mammary Ductal Morphogenesis, and Its Absence Reveals Alternative Cell Death MechanismsDevelopmental Cell, 2007