title: 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.affiliation: Department of Biochemistry and Molecular Biology, George Washington University, Washington, DC 20037, USA. bcmmxw@gwumc.edu
authors.forename: Mei-Yi
authors.initials: MY
authors.lastname: Wu
authors.forename: Junjiang
authors.initials: J
authors.lastname: Fu
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
authors.forename: Ray-Chang
authors.initials: RC
authors.lastname: Wu
mesh_terms: D000818:Animals; D001343:Autophagy; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D056921:Nuclear Receptor Coactivator 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism / Q000627:therapeutic use; D012795:Sialoglycoproteins / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008263:Macrophage Migration-Inhibitory Factors; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D012795:Sialoglycoproteins; C571744:bone sialoprotein (35-62), human; D056921:Nuclear Receptor Coactivator 3; D051550:I-kappa B Kinase