Steroid receptor coactivator 3 regulates autophagy in breast cancer cells through macrophage migration inhibitory factor.

Abstract	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.
Authors	Mei-Yi Wu, Junjiang Fu, Jianming Xu, Bert W O'Malley, Ray-Chang Wu
Journal	Cell research (Cell Res) Vol. 22 Issue 6 Pg. 1003-21 (Jun 2012) ISSN: 1748-7838 [Electronic] England
PMID	22430150 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Hypoxia-Inducible Factor 1, alpha Subunit Macrophage Migration-Inhibitory Factors Peptide Fragments RNA, Small Interfering Sialoglycoproteins bone sialoprotein (35-62), human Nuclear Receptor Coactivator 3 I-kappa B Kinase
Topics	Animals Autophagy Breast Neoplasms (drug therapy, metabolism, pathology) Cell Hypoxia Cell Line, Tumor Cell Survival Female HEK293 Cells HeLa Cells Humans Hypoxia-Inducible Factor 1, alpha Subunit (metabolism) I-kappa B Kinase (metabolism) Macrophage Migration-Inhibitory Factors (antagonists & inhibitors, genetics, metabolism) Mice Nuclear Receptor Coactivator 3 (antagonists & inhibitors, genetics, metabolism) Peptide Fragments (metabolism) Phosphorylation Promoter Regions, Genetic RNA Interference RNA, Small Interfering (metabolism, therapeutic use) Sialoglycoproteins (metabolism) Transplantation, Heterologous

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