Anticarin-beta shows a promising anti-osteosarcoma effect by specifically inhibiting CCT4 to impair proteostasis

doi:10.1016/j.apsb.2021.12.024

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	Anticarin-beta shows a promising anti-osteosarcoma effect by specifically inhibiting CCT4 to impair proteostasis
	Wang, Gan; Zhang, Min; Meng, Ping; Long, Chengbo; Luo, Xiaodong; Yang, Xingwei; Wang, Yunfei; Zhang, Zhiye; Mwangi, James; Kamau, Peter Muiruri; Dai, Zhi; Ke, Zunfu; Zhang, Yi; Chen, Wenlin; Zhao, Xudong; Ge, Fei; Lv, Qiumin; Rong, Mingqiang; Li, Dongsheng; Jin, Yang; Sheng, Xia; Lai, Ren
	2022
发表期刊	ACTA PHARMACEUTICA SINICA B
卷号	12 期号:5 页码:2268-2279
摘要	Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-beta that can specifically bind to and inhibit CCT4. Anticarin-beta shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-beta potently impedes CCT4-mediated STAT3 maturation. Anticarin-beta displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
关键词	Proteostasis CCT TRiC Osteosarcoma STAT3 Anticarin-beta PDX model CYTOSOLIC CHAPERONIN CANCER-CELLS COMPLEX EXPRESSION SURVIVAL PROTEIN TUBULIN GROWTH
DOI	10.1016/j.apsb.2021.12.024
收录类别	SCI
WOS记录号	WOS:000810889400009
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74772
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Wang, Gan,Zhang, Min,Meng, Ping,et al. Anticarin-beta shows a promising anti-osteosarcoma effect by specifically inhibiting CCT4 to impair proteostasis[J]. ACTA PHARMACEUTICA SINICA B,2022,12(5):2268-2279.
APA	Wang, Gan.,Zhang, Min.,Meng, Ping.,Long, Chengbo.,Luo, Xiaodong.,...&Lai, Ren.(2022).Anticarin-beta shows a promising anti-osteosarcoma effect by specifically inhibiting CCT4 to impair proteostasis.ACTA PHARMACEUTICA SINICA B,12(5),2268-2279.
MLA	Wang, Gan,et al."Anticarin-beta shows a promising anti-osteosarcoma effect by specifically inhibiting CCT4 to impair proteostasis".ACTA PHARMACEUTICA SINICA B 12.5(2022):2268-2279.

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