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Mesenchymal to epithelial reverting transition: a key role for re-expression of E-cadherin

Chao, Yvonne Lai (2011) Mesenchymal to epithelial reverting transition: a key role for re-expression of E-cadherin. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Metastasis is a major contributor to breast cancer mortality, as currently available therapies are unable to ensure progression or disease-free survival. Little is known about the molecular pathogenesis of metastasis, and the role of the surrounding microenvironment is only beginning to be understood. In vitro studies have repeatedly shown that epithelial to mesenchymal transition (EMT) and loss of E-cadherin expression are critical events in the initiation of metastasis and can be induced by the microenvironment. However, metastases are often well-differentiated and epithelial in phenotype, suggesting that EMT is reversible. The role of E-cadherin expression and mesenchymal to epithelial reverting transition (MErT) in metastatic colonization of the secondary site remains ill-defined. Evidence for E-cadherin re-expression and partial MErT was observed in metastases of breast and prostate cancer patients, and suggests that MErT is unstable and reversible. MDA-MB-231 breast cancer cells cultured with hepatocytes also resulted in E-cadherin re-expression and partial MErT, suggesting that such phenotypic plasticity can be induced by the microenvironment of the liver, a key site of breast cancer metastases. Re-expression of E-cadherin following hepatocyte coculture not only results in heterotypic ligation between cancer and liver parenchymal cells, but also activates Erk survival signaling and increases resistance to nutrient-deprivation and chemotherapy. Taken together, our results indicate that the distant organ microenvironment may induce E-cadherin re-expression and partial MErT to enhance the survival of metastatic cancer cells at the secondary organ.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Chao, Yvonne Laichao.yvonne@medstudent.pitt.eduYLC3
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairStrom, Stephenstrom@pitt.eduSTROM
Committee MemberWells, Alanwellsa@upmc.eduAHW6
Committee MemberGerlach, Jorgjgerlach@pitt.eduJGERLACH
Committee MemberDeFrances, Mariedefrancesmc@upmc.eduMCD14
Committee MemberZarnegar, Rezarezazar@pitt.eduREZAZAR
Date: 9 March 2011
Date Type: Completion
Defense Date: 24 February 2011
Approval Date: 9 March 2011
Submission Date: 28 February 2011
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: breast cancer; E-cadherin; metastasis
Other ID:, etd-02282011-124755
Date Deposited: 10 Nov 2011 19:31
Last Modified: 19 Dec 2016 14:34


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