Adhikary, A. and Chakraborty, S. and Mazumdar, M. and Ghosh, S. and Mukherjee , S. and Manna, A and Mohanty, S. and Nakka , N.N. and Joshi , S. and De , A. and Chattopadhyay , S. and Sa G,, G. and Das , T. (2014) Inhibition of Epithelial to Mesenchymal Transition by E-cadherin Up-regulation via Repression of Slug Transcription and Inhibition of E-cadherin Degradation. The Journal fo Biological Chemistry (JBC), 289 (37). pp. 25431-25444. ISSN SEPTEMBER 12, 2014•VOLUME 289•NUMBER 37

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Abstract

The evolution of the cancer cell into a metastatic entity is the major cause of death in patients with cancer. It has been acknowledged that aberrant activation of a latent embryonic program, known as the epithelial-mesenchymal transition (EMT), can endow cancer cells with the migratory and invasive capabilities associated with metastatic competence for which E-cadherin switch is a well-established hallmark. Discerning the molecular mechanisms that regulate E-cadherin expression is therefore critical for understanding tumor invasiveness and metastasis. Here we report that SMAR1 overexpression inhibits EMT and decelerates the migratory potential of breast cancer cells by up-regulating E-cadherin in a bidirectional manner. While SMAR1-dependent transcriptional repression of Slug by direct recruitment of SMAR1/HDAC1 complex to the matrix attachment region site present in the Slug promoter restores E-cadherin expression,SMAR1also hinders E-cadherin-MDM2 interaction thereby reducing ubiquitination and degradation of E-cadherin protein. Consistently, siRNA knockdown of SMAR1 expression in these breast cancer cells results in a coordinative action of Slug-mediated repression of E-cadherin transcription, as well as degradation of E-cadherin protein through MDM2, up-regulating breast cancer cell migration. These results indicate a crucial role for SMAR1 in restraining breast cancer cell migration and suggest the candidature of this scaffold matrixassociated region-binding protein as a tumor suppressor.

Item Type:	Article
Additional Information:	This is online free article for full text click above weblink
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	28 Apr 2015 04:12
Last Modified:	26 May 2016 07:45
URI:	http://nccs.sciencecentral.in/id/eprint/148

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