Abstract
CCT5, a subunit of the chaperonin-containing TCP1 complex, has been implicated in the development of various malignancies. However, its role in bladder cancer remains undefined. This study investigated the functional contribution of CCT5 and its association with Hippo/YAP signaling. Using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), CCT5 expression and its prognostic significance were analyzed. Single-cell and spatial transcriptomics were employed to explore expression patterns and cellular heterogeneity. Functional assessments were conducted in vitro and in vivo using xenografts. To elucidate the underlying mechanisms, RNA-seq was integrated with Western blotting analysis. CCT5 was found to be upregulated in bladder cancer and correlated with poor prognosis and aggressive pathological features. Single-cell and spatial analyses revealed that CCT5 was enriched in malignant epithelial subpopulations with high CNV scores, activated oncogenic pathways, and extensive cell-cell interactions. Functionally, CCT5 promoted proliferation, migration, invasion, and G1/S transition while inhibiting apoptosis; its depletion reduced xenograft growth. At the signaling level, CCT5 knockdown enhanced phosphorylation of MST1, LATS1, and YAP, without significant changes in total protein levels, suggesting activation of Hippo/YAP signaling. These findings highlight CCT5 as an oncogenic factor in bladder cancer, potentially acting through the regulation of Hippo/YAP signaling, and propose its potential as a biomarker and therapeutic target in bladder cancer.