Chaperonin-Containing TCP-1 Promotes Cancer Chemoresistance and Metastasis through the AKT-GSK3?-?-Catenin and XIAP-Survivin Pathways.

ABSTRACT: Chaperonin-containing TCP-1 (CCT) is a chaperonin composed of eight subunits that participates in intracellular protein folding. Here, we showed that increased levels of subunits of CCT, particularly CCT-?, were significantly correlated with lower survival rates for cancer patients. Endogenously high expression of CCT-? was found in cancer cell lines, such as the triple-negative breast cancer cell line MDA-MB-231 and the highly metastatic non-small-cell lung cancer cell line CL1-5. Knocking down CCT-? in these cancer cells led to decreased levels of anti-apoptotic proteins, such as XIAP, as well as inhibited phosphorylation of Ser473-AKT and GSK3, resulting in decrease of the nucleus-entering form of ?-catenin; these changes reduced the chemoresistance and migration/invasion of the cells. Conversely, overexpression of CCT-? recovered the chemoresistance and cell migration/invasion by promoting the AKT-GSK3?-?-catenin and XIAP-Survivin pathways. Coimmunoprecipitation data revealed that the CCT complex might directly bind and stabilize XIAP and ?-catenin. This study not only elucidates the roles of CCT in chemoresistance and metastasis, which are two major obstacles for current cancer therapy, but also provides a possible therapeutic strategy against cancers with overexpressed CCT-?.

SUBMITTER: Chang YX 

PROVIDER: S-EPMC7767469 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature