Prognostic significance of CCT5 in breast cancer and its regulatory mechanisms in promoting tumorigenesis

This study explored the prognostic significance, biological functions, and molecular mechanisms of the chaperone CCT5 in breast cancer (BC), aiming to provide a theoretical basis for prognosis and targeted therapy. Key dependency genes in BC were screened via the DepMap database. Differential expression and prognostic analyses were performed using TCGA and GEO datasets, identifying CCT5 as the target gene. CCT5 expression in BC clinical tissues was validated by qRT-PCR, Western blot, and immunohistochemistry, followed by correlation analyses with clinical characteristics and prognosis. Stable CCT5 overexpression and knockdown cell models were established to assess effects on proliferation, migration, and invasion. WGCNA and enrichment analyses explored potential mechanisms, while Western blot and Nutlin-3 rescue assays verified regulation of the p53 pathway, with in vivo xenograft models used for final validation. CCT5 acted as a core dependency gene supporting BC cell survival. High CCT5 expression was significantly associated with poorer overall and disease-free survival, and correlated with larger tumor size, higher histological grade, positive lymph node metastasis, HER2-positive status, and elevated Ki-67 index. Functional assays showed that CCT5 overexpression enhanced proliferation, migration, and invasion, whereas knockdown suppressed these phenotypes. Mechanistically, CCT5 facilitated BC progression via negative regulation of the p53 pathway. Rescue experiments and in vivo xenograft models confirmed that the p53 activator Nutlin-3 reversed both p53 pathway inhibition and the oncogenic effects driven by CCT5 overexpression. High CCT5 expression is associated with poor prognosis. CCT5 functions as a key oncogene in BC and drives tumor progression through negative regulation of the p53 signaling pathway. This study provides comprehensive insights into the role and mechanisms of CCT5 in BC, thereby offering theoretical support for its potential as a therapeutic target.