title: Molecular chaperone CCT3 supports proper mitotic progression and cell proliferation in hepatocellular carcinoma cells.
abstract: CCT3 was one of the subunits of molecular chaperone CCT/TRiC complex, which plays a central role in maintaining cellular proteostasis. We demonstrated that expressions of CCT3 mRNA and protein are highly up-regulated in hepatocellular carcinoma (HCC) tissues, and high level of CCT3 is correlated with poor survival in cancer patients. In HCC cell lines, CCT3 depletion suppresses cell proliferation by inducing mitotic arrest at prometaphase and apoptosis eventually. We also identified CCT3 as a novel regulator of spindle integrity and as a requirement for proper kinetochore-microtubule attachment during mitosis. Moreover, we found that CCT3 depletion sensitizes HCC cells to microtubule destabilizing drug Vincristine. Collectively, our study suggests that CCT3 is indispensible for HCC cell proliferation, and provides a potential drug target for treatment of HCC.
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China.
authors.forename: Youheng
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China.
authors.forename: Jiaxue
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China.
authors.forename: Pingzhao
authors.initials: P
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China.
authors.forename: Suqin
authors.initials: S
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China.
authors.forename: Hexige
authors.initials: H
authors.lastname: Saiyin
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China.
authors.forename: Reziya
authors.initials: R
authors.lastname: Wumaier
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China.
authors.forename: Xianmei
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China. Electronic address: chenjiwang@fudan.edu.cn.
authors.forename: Chenji
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China. Electronic address: longyu@fudan.edu.cn.
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation / Q000187:drug effects; D056404:Chaperonin Containing TCP-1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008938:Mitosis / Q000187:drug effects; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D050257:Tubulin Modulators / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C533299:CCT3 protein, human; D012333:RNA, Messenger; D050257:Tubulin Modulators; D014750:Vincristine; D056404:Chaperonin Containing TCP-1
keywords: CCT3; Chaperonin; Hepatocellular carcinoma; Microtubule; Vincristine