期刊
CELL CHEMICAL BIOLOGY
卷 29, 期 3, 页码 373-+出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2021.10.006
关键词
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资金
- National Program on Key Basic Research Project of China [2016YFA0501900, 2016YFA0501904]
- National Natural Science Foundation of China [32071245, 31671428]
- Natural Science Foundation of Shanghai [20ZR1474400]
- Shanghai Municipal Science and Technology Major Project [2019SHZDZX02]
This study discovered STAT3 as a direct functional protein target of rapamycin using a chemical proteomics strategy. Rapamycin inhibits tumor growth in hepatocellular carcinoma by suppressing c-Myc-regulated gene expression. These findings provide important information for the development of STAT3 inhibitors for cancer therapy.
Rapamycin is widely recognized as an inhibitor of mTOR, and has been approved for clinical use as an immunosuppressant. Its potencies in anti-cancer, anti-aging, and neurodegenerative diseases are emergingly established. The exploration of other targets of rapamycin will further elucidate its underlying mechanisms of action. In this study, we use a chemical proteomics strategy that has identified STAT3, a transcription factor considered to be undruggable, as a direct functional protein target of rapamycin. Together with other multi-dimensional proteomics data, we show that rapamycin treatment in cell culture significantly inhibits c-Myc-regulated gene expression. Furthermore, we show that rapamycin suppresses tumor growth along with a decreased expression of STAT3 and c-Myc in an in vivo xenograft mouse model for hepatocellular carcinoma. Our data suggest that rapamycin acts directly on STAT3 to decrease its transcription activity, providing important information for the pharmacological and pharmaceutical development of STAT3 inhibitors for cancer therapy.
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