Cct6a, also known as Chaperonin Containing TCP1 Subunit 6A, is a molecular chaperone involved in the folding and stabilization of newly synthesized proteins. It participates in various biological processes and is associated with multiple pathways. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying its functions [1,2,3,4,5,6,7,8,9,10].

In multiple cancer types, Cct6a shows significant implications. In lung adenocarcinoma, silencing Cct6a inhibits cell proliferation, migration, and promotes apoptosis. It interacts with STAT1, enhancing its stability, which in turn promotes HK2 transcription and aerobic glycolysis [1]. In osteosarcoma, Cct6a knockdown attenuates cell growth, viability, survival, and induces apoptosis, also suppressing the Akt pathway [3]. In colon cancer, Cct6a silencing suppresses proliferation and survival in vitro and in vivo, and it targets BIRC5 differently depending on p53 status [4]. In Ewing sarcoma, high Cct6a expression is associated with poor prognosis, making it a potential prognostic biomarker [5]. In esophageal squamous cell carcinoma, Cct6a promotes cell proliferation, invasion, and epithelial-mesenchymal transition by activating the TGF-β/Smad/c-Myc pathway [6]. In hepatocellular carcinoma, high Cct6a expression is related to tumor features and poor prognosis [7]. In colorectal cancer, knockout of Cct6a reduces cell proliferation and migration [8]. In lung adenocarcinoma, Cct6a is co-amplified and co-expressed with EGFR, and its overexpression is associated with unfavorable outcomes [9]. In osteosarcoma, Cct6a is associated with CDC20, Enneking stage, and prognosis, and its knockdown suppresses cell viability and invasion [10].

In conclusion, Cct6a is a crucial gene in protein folding. Model-based research, especially KO/CKO mouse models if applicable, has revealed its significant roles in various cancer-related processes, such as cell proliferation, apoptosis, invasion, and metabolism. These findings highlight Cct6a as a potential target for cancer therapy and a biomarker for prognosis prediction in multiple cancer types.

References:

1. Yu, Shao-Kun, Yu, Tao, Wang, Yu-Ming, Liu, Jia, Lu, Kai-Hua. 2024. CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis. In Journal of translational medicine, 22, 460. doi:10.1186/s12967-024-05284-7. https://pubmed.ncbi.nlm.nih.gov/38750462/

2. Yan, Peishuo, Yang, Kun, Xu, Mengwei, Wang, Lan, Yu, Guoying. . CCT6A alleviates pulmonary fibrosis by inhibiting HIF-1α-mediated lactate production. In Journal of molecular cell biology, 16, . doi:10.1093/jmcb/mjae021. https://pubmed.ncbi.nlm.nih.gov/38760881/

3. Zeng, Weiquan, Wu, Meizhu, Cheng, Ying, Peng, Jun, Shen, Aling. 2022. CCT6A knockdown suppresses osteosarcoma cell growth and Akt pathway activation in vitro. In PloS one, 17, e0279851. doi:10.1371/journal.pone.0279851. https://pubmed.ncbi.nlm.nih.gov/36584147/

4. Zhang, Han, Zheng, Taotao, Qin, Chuan, Bian, Chunxiang, Liu, Huawen. 2024. CCT6A promotes cell proliferation in colon cancer by targeting BIRC5 associated with p53 status. In Cancer gene therapy, 31, 1151-1163. doi:10.1038/s41417-024-00806-3. https://pubmed.ncbi.nlm.nih.gov/38997438/

5. Jiang, Jie, Liu, Chong, Xu, Guoyong, Li, Hao, Zhan, Xinli. . CCT6A, a novel prognostic biomarker for Ewing sarcoma. In Medicine, 100, e24484. doi:10.1097/MD.0000000000024484. https://pubmed.ncbi.nlm.nih.gov/33530265/

6. Xia, Xiuli, Zhao, Shushan, Chen, Wenting, Xu, Chao, Zhao, Dongqiang. 2023. CCT6A promotes esophageal squamous cell carcinoma cell proliferation, invasion and epithelial-mesenchymal transition by activating TGF-β/Smad/c-Myc pathway. In Irish journal of medical science, 192, 2653-2660. doi:10.1007/s11845-023-03357-y. https://pubmed.ncbi.nlm.nih.gov/37017854/

7. Cai, Yue, Wu, Deng, Zhan, Lei. 2021. CCT6A expression in hepatocellular carcinoma and its correlation with clinical characteristics, liver function indexes, tumor markers and prognosis. In Clinics and research in hepatology and gastroenterology, 46, 101796. doi:10.1016/j.clinre.2021.101796. https://pubmed.ncbi.nlm.nih.gov/34500119/

8. Ma, Jianxing, Wei, Qiuya, Zhang, Lili, Yan, Siyuan, Wang, Chen. 2024. CCT6A functions as promising diagnostic biomarker and promotes cell proliferation in colorectal cancer. In Journal of Cancer, 15, 5897-5909. doi:10.7150/jca.98901. https://pubmed.ncbi.nlm.nih.gov/39440061/

9. Wang, Haiwei, Wang, Xinrui, Xu, Liangpu, Lin, Yingying, Zhang, Ji. 2022. CCT6A and CHCHD2 Are Coamplified with EGFR and Associated with the Unfavorable Clinical Outcomes of Lung Adenocarcinoma. In Disease markers, 2022, 1560199. doi:10.1155/2022/1560199. https://pubmed.ncbi.nlm.nih.gov/35937942/

10. Wang, Ning, Chen, Yong, Wu, Jie. 2023. CCT6A is associated with CDC20, Enneking stage and prognosis in osteosarcoma, and its knockdown suppresses osteosarcoma cell viability and invasion. In Oncology letters, 25, 201. doi:10.3892/ol.2023.13787. https://pubmed.ncbi.nlm.nih.gov/37113398/