Please use this identifier to cite or link to this item:
Title: Induction of ZEB proteins by inactivation of RB protein is key determinant of mesenchymal phenotype of breast cancer
Authors: Arima, Y.
Hayashi, H.
Sasaki, M.
Hosonaga, M.
Goto, T.M.
Chiyoda, T.
Kuninaka, S.
Shibata, T.
Ohata, H.
Nakagama, H.
Taya, Y. 
Saya, H.
Issue Date: 9-Mar-2012
Citation: Arima, Y., Hayashi, H., Sasaki, M., Hosonaga, M., Goto, T.M., Chiyoda, T., Kuninaka, S., Shibata, T., Ohata, H., Nakagama, H., Taya, Y., Saya, H. (2012-03-09). Induction of ZEB proteins by inactivation of RB protein is key determinant of mesenchymal phenotype of breast cancer. Journal of Biological Chemistry 287 (11) : 7896-7906. ScholarBank@NUS Repository.
Abstract: Wepreviously showed that depletion of the retinoblastoma protein (RB) induces down-regulation of the adhesion molecule E-cadherin and thereby triggers the epithelial-mesenchymal transition. To further characterize the effect of RB inactivation on the phenotype of cancer cells, we have now examined RB expression in human breast cancer cell lines and clinical specimens. We found that RB-inactive cells exhibit a mesenchymal-like morphology and are highly invasive. We also found that ZEB proteins, transcriptional repressors of the E-cadherin gene, are markedly up-regulated in these cells in a manner sensitive to the miR-200 family of microRNAs. Moreover, depletion of ZEB in RB-inactive cells suppressed cell invasiveness and proliferation and induced epithelial marker expression. These results implicate ZEB in induction of the epithelial-mesenchymal transition, as well as in maintenance of the mesenchymal phenotype in RB-inactive cells. We also developed a screening program for inhibitors of ZEB1 expression and thereby identified several cyclin-dependent kinase inhibitors that blocked both ZEB1 expression and RB phosphorylation. Together, our findings suggest that RB inactivation contributes to tumor progression not only through loss of cell cycle control but also through up-regulation of ZEB expression and induction of an invasive phenotype. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
ISSN: 00219258
DOI: 10.1074/jbc.M111.313759
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Sep 23, 2022


checked on Sep 23, 2022

Page view(s)

checked on Sep 22, 2022

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.