2. Academic Validation
  3. Rapamycin targets STAT3 and impacts c-Myc to suppress tumor growth

Rapamycin targets STAT3 and impacts c-Myc to suppress tumor growth

  • Cell Chem Biol. 2022 Mar 17;29(3):373-385.e6. doi: 10.1016/j.chembiol.2021.10.006.
Le Sun 1,  Yu Yan 2,  Heng Lv 1,  Jianlong Li 1,  Zhiyuan Wang 1,  Kun Wang 1,  Lin Wang 3,  Yunxia Li 2,  Hong Jiang 2,  Yaoyang Zhang 4
Affiliations

Affiliations

  • 1 Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Road, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Road, Shanghai 201210, China.
  • 3 ShanghaiTech University, Shanghai 201210, China.
  • 4 Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Road, Shanghai 201210, China. Electronic address: zyy@sioc.ac.cn.
PMID: 34706270 DOI: 10.1016/j.chembiol.2021.10.006
Abstract

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.

Keywords

STAT3; c-Myc; cancer; chemical proteomics; rapamycin.

Figures
Products