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.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-11212007-113407 |
| Date | 26 November 2007 |
| Creators | Shepard, Christopher Reed |
| Contributors | Donna Stolz, PhD, Adam Brufsky, MD PhD, Linda Griffith, PhD, Paul Monga, MD, Alan Wells, MD DMSc |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-11212007-113407/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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