Volume 22, No 6, Jun 2012
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 22 Issue 6, June 2012: 1003-1021
ORIGINAL ARTICLES
Steroid receptor coactivator 3 regulates autophagy in breast cancer cells through macrophage migration inhibitory factor
Mei-Yi Wu 1, Junjiang Fu 2, Jianming Xu 3, Bert W O'Malley3 and Ray-Chang Wu 1,3
1Department of Biochemistry and Molecular Biology, George Washington University, Washington, DC 20037, USA
2The Research Center for Preclinical Medicine, Luzhou Medical College, Luzhou City, Sichuan 646000, China
3Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Correspondence: Mei-Yi Wu(bcmmxw@gwumc.edu)
SRC-3/AIB1 (steroid receptor coactivator 3/amplified in breast cancer 1) is an authentic oncogene that contributes to the development of drug resistance and poor disease-free survival in cancer patients. Autophagy is also an important cell death mechanism that has tumor suppressor function. In this study, we identified macrophage migration inhibitory factor (MIF) as a novel target gene of SRC-3 and demonstrated its importance in cell survival. Specifically, we showed that MIF is a strong suppressor of autophagic cell death. We further showed that suppression of MIF, in turn, induced autophagic cell death, enhanced chemosensitivity and inhibited tumorigenesis in a xenograft mouse tumorigenesis model. Our study demonstrated that regulation of MIF expression and suppression of autophagic cell death is a potent mechanism by which SRC-3 contributes to increased chemoresistance and tumorigenicity.
10.1038/cr.2012.44; published online 20 March 2012
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