期刊
CELL RESEARCH
卷 22, 期 6, 页码 1003-1021出版社
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2012.44
关键词
SRC-3; MIF; autophagy; tumorigenesis; chemosensitivity
类别
资金
- Dan L Duncan Cancer Center
- Baylor College of Medicine
- Susan G Komen for the Cure [BCTR0707225]
- NIH [R01 CA119689]
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.
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