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» Articles » PMID: 25698877

Regulation of Epithelial-mesenchymal Transition in Breast Cancer Cells by Cell Contact and Adhesion

Overview
Journal Cancer Inform
Publisher Sage Publications
Specialty Biomedical Engineering
Date 2015 Feb 21
PMID 25698877
Citations 31
Authors
Magdalena A Cichon
Celeste M Nelson
Derek C Radisky
Affiliations
Soon will be listed here.
Abstract

Epithelial-mesenchymal transition (EMT) is a physiological program that is activated during cancer cell invasion and metastasis. We show here that EMT-related processes are linked to a broad and conserved program of transcriptional alterations that are influenced by cell contact and adhesion. Using cultured human breast cancer and mouse mammary epithelial cells, we find that reduced cell density, conditions under which cell contact is reduced, leads to reduced expression of genes associated with mammary epithelial cell differentiation and increased expression of genes associated with breast cancer. We further find that treatment of cells with matrix metalloproteinase-3 (MMP-3), an inducer of EMT, interrupts a defined subset of cell contact-regulated genes, including genes encoding a variety of RNA splicing proteins known to regulate the expression of Rac1b, an activated splice isoform of Rac1 known to be a key mediator of MMP-3-induced EMT in breast, lung, and pancreas. These results provide new insights into how MMPs act in cancer progression and how loss of cell-cell interactions is a key step in the earliest stages of cancer development.

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