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EPITHELIAL CADHERIN RE-EXPRESSION IN METASTATIC BREAST CANCER AS A STRATEGY FOR METASTATIC COLONIZATION OF THE LIVER

by Shepard, Christopher Reed

Abstract (Summary)
Epithelial-cadherin downregulation enables cancer cells to escape from the primary mass; however, E-cadherin has been found to be expressed on metastatic foci, bringing into question the role of this molecule in tumor progression. We define a novel role for the cellular adhesion molecule E-cadherin, in which the proteins re-emergence promotes carcinoma-parenchymal interactions in ectopic sites. Non-metastatic E-cadherin positive MCF7 breast cancer cells form heterotypic cohesions mediated by E-cadherin, and in invasive and metastatic MDA-MB-231 cells, the E-cadherin promoter hypermethylation that prevents endogenous E-cadherin expression is reversed when these cells are cultured with hepatocytes. The function of this re-expression is suggested by the E-cadherin-dependent sustained activation of Erk-MAP kinase and Akt in these breast carcinoma cells. Thus, we propose that E-cadherin expression and subsequent heterocellular interactions direct cell fate decisions that may ultimately enable colonization of a secondary site by an invasive cancer cell.
Bibliographical Information:

Advisor:Donna Stolz, PhD; Adam Brufsky, MD PhD; Linda Griffith, PhD; Paul Monga, MD; Alan Wells, MD DMSc

School:University of Pittsburgh

School Location:USA - Pennsylvania

Source Type:Master's Thesis

Keywords:cellular and molecular pathology

ISBN:

Date of Publication:11/26/2007

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