Adhikary, Arghya ; Chakraborty, Samik ; Mazumdar, Minakshi ; Ghosh, Swatilekha ; Mukherjee, Shravanti ; Manna, Argha ; Mohanty, Suchismita ; Nakka, Kiran Kumar ; Joshi, Shruti ; De, Abhijit ; Chattopadhyay, Samit ; Sa, Gaurisankar ; Das, Tanya (2014) Inhibition of Epithelial to Mesenchymal Transition by E-cadherin Up-regulation via Repression of Slug Transcription and Inhibition of E-cadherin Degradation Journal of Biological Chemistry, 289 (37). pp. 25431-25444. ISSN 00219258
![]() |
PDF
2MB |
Official URL: http://doi.org/10.1074/jbc.M113.527267
Related URL: http://dx.doi.org/10.1074/jbc.M113.527267
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, SMAR1 also 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 matrix-associated region-binding protein as a tumor suppressor.
Item Type: | Article |
---|---|
Source: | Copyright of this article belongs to Elsevier Inc |
ID Code: | 134536 |
Deposited On: | 09 Jan 2023 04:03 |
Last Modified: | 09 Jan 2023 04:03 |
Repository Staff Only: item control page