CCT6A Promotes Colon Cancer Cell Proliferation, Migration, and Invasion by Modulating Fatty Acid Metabolism and Activating the TGF-β1/Smad Signaling Pathway.

Colon cancer treatment remains a clinical challenge. Chaperonin containing TCP1 subunit 6 A (CCT6A) acts as an oncogene in multiple tumors. In this study, we investigated its roles in colon cancer cells. We analyzed CCT6A expression using single-cell datasets and the Gene Expression Profiling Interactive Analysis based on The Cancer Genome Atlas database. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and western blot analysis were used to assess CCT6A expression levels in colon cancer tissues and cell lines. Additionally, specific roles of CCT6A in colon cancer was analyzed using cell counting kit-8, 5-ethynyl-2'-deoxyuridine staining, flow cytometry, wound healing, transwell, boron dipyrromethene staining, western blot analysis, and nude model mice. We found that CCT6A expression levels were significantly elevated in colon cancer tissues compared to those in normal tissues and predicted a worse prognosis. CCT6A induced proliferation, migration, invasion, epithelial-mesenchymal transition, and fatty acid synthesis and suppressed apoptosis in colon cancer cells. Mechanistically, CCT6A promoted colon cancer progression by increasing the cleavage of latency-associated peptide (LAP)-transforming growth factor-β1 (TGF-β1) to mature form of TGF-β and inducing Smad2/3 phosphorylation in colon cancer cells. Overall, CCT6A promoted colon cancer progression by modulating fatty acid metabolism and activating the TGF-β1/Smad signaling, serving as a potential therapeutic target for colon cancer.