Molecular chaperone CCT3 supports proper mitotic progression and cell proliferation in hepatocellular carcinoma cells

Cancer Lett. 2016 Mar 1;372(1):101-9. doi: 10.1016/j.canlet.2015.12.029. Epub 2015 Dec 29.

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.

Keywords: CCT3; Chaperonin; Hepatocellular carcinoma; Microtubule; Vincristine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle Checkpoints
  • Cell Proliferation* / drug effects
  • Chaperonin Containing TCP-1 / genetics
  • Chaperonin Containing TCP-1 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Mitosis* / drug effects
  • RNA Interference
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tubulin Modulators / pharmacology
  • Vincristine / pharmacology

Substances

  • Antineoplastic Agents, Phytogenic
  • CCT3 protein, human
  • RNA, Messenger
  • Tubulin Modulators
  • Vincristine
  • Chaperonin Containing TCP-1