Shepard, Christopher Reed
(2007)
EPITHELIAL CADHERIN RE-EXPRESSION IN METASTATIC BREAST CANCER AS A STRATEGY FOR METASTATIC COLONIZATION OF THE LIVER.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
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 protein's 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.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Shepard, Christopher Reed | crs32@pitt.edu | CRS32 | |
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| ETD Committee: |
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| Date: |
26 November 2007 |
| Date Type: |
Completion |
| Defense Date: |
25 October 2007 |
| Approval Date: |
26 November 2007 |
| Submission Date: |
21 November 2007 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Cellular and Molecular Pathology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
tumor cell dormancy; E-cadherin; invasive breast cancer |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-11212007-113407/, etd-11212007-113407 |
| Date Deposited: |
10 Nov 2011 20:05 |
| Last Modified: |
19 Dec 2016 14:37 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/9750 |
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