Journal
CELLULAR SIGNALLING
Volume 29, Issue -, Pages 209-217Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2016.11.001
Keywords
Chemotherapy; YAP; Protein stability; Transformative phenotypes; beta TrCP
Categories
Funding
- National Natural Science Foundation of China [81472124, 31171086, 81202958, 81672332]
- Shanghai Municipal Science and Technology Commission [14YF1412300]
- Shanghai Municipal Commission of Health and Family Planning Foundation [20114Y009]
- China central colleges and universities basic research-specific cross discipline grant [1501219096]
- Outstanding Youth Training Program of Tongji University [2013KJ065]
Ask authors/readers for more resources
Chemotherapy is critical for the treatment of liver cancer. Despite the pro-apoptotic effects of corosolic acid (CA) have been revealed, the methods to enhance its efficacy are unclear. The aim of this study is to investigate the target that might reduce CA efficacy and figure out the way to conquer it. We found reduction of Yes-associated protein (YAP) might be a critical event that suppresses efficacy of CA. Treatment of CA accelerated degradation of YAP via enhancing its phosphorylation by LATS1. Moreover, we found CA boosts beta TrCP-dependent Ubiquitination of YAP. Interestingly, the protein stability of beta TrCP per se could be enhanced by CA. Notably, ActionomycinD (AD) strengthened CA-induced apoptosis of liver cancer cells via elevating YAP while down-regulating beta TrCP. Importantly, combined treatment of CA and AD had much more obvious influences against trans formative phenotypes of liver cancer cells than those under treatment of CA alone. Combined usage of AD successfully reduced IC50 value of CA. In summary, we have first uncovered that suppression of YAP might reduce efficacy of CA to treat liver cancer, combined treatment of AD and CA might solve this problem. (C) 2016 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available