CCT3-mediated regulation of XPO1/RB1 axis stability promotes cellular senescence and tumor progression in clear cell renal carcinoma.

ABSTRACT: Cellular senescence's role in clear cell renal carcinoma (ccRCC) remains unclear. We identify CCT3 as a driver of ccRCC progression by enhancing XPO1 stability via correct folding, confirmed by Co-IP and GST pull-down. This promotes nuclear export of tumor suppressors such as RB1 and p21, suppressing cellular senescence. Indeed, experimental evidence showed significantly reduced senescence-associated β-galactosidase (SA-β-gal) activity and altered expression patterns of senescence markers (e.g., p21, CDK4, and cyclin D) in the presence of increased CCT3. Functionally, CCT3 depletion induced robust G1 phase arrest, promoted cellular senescence, and markedly diminished ccRCC cell proliferation, migration, and invasion in vitro. Crucially, in vivo studies demonstrated that the c

SUBMITTER: Cao Y 

PROVIDER: S-EPMC12924737 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature