Cct4, a member of the chaperonin containing TCP1 complex, is a key component of the CCT chaperone complex. It is involved in protein folding, and is associated with pathways like mTOR signaling [1]. CCT4 has been found to be important in maintaining proteostasis, a crucial biological process for cell survival and function [5].

In various cancers, CCT4 has shown significant roles. In glioblastoma, YB-1 protein binds to the 5'UTR of CCT4 mRNA to promote its translation, which in turn activates the mTOR signaling pathway, promoting tumor growth [1]. In esophageal squamous cell carcinoma, CCT4 is highly expressed, and its knockdown inhibits glycolysis, enhances cisplatin sensitivity, and affects cell proliferation, migration, apoptosis, and cell cycle [2]. In hepatocellular carcinoma, CCT4 is upregulated, and its knockdown inhibits tumor cell proliferation, induces apoptosis, and interacts with Cdc20 to regulate anaphase-promoting complex activity [3]. In breast cancer, CCT4 is overexpressed and is involved in the LINC01234/hsa-miR-30c-2-3p/CCT4/mTOR axis, promoting malignant behaviors of cancer cells [6]. In contrast, in Wilms tumor, CCT4 is downregulated and may play a reverse regulatory role, potentially through the ErbB signaling pathway [4]. Also, a compound anticarin-β can specifically bind to and inhibit CCT4, showing anti-osteosarcoma effects by impairing proteostasis [5].

In conclusion, CCT4 plays essential roles in protein folding and is intricately involved in multiple cancer-related biological processes. The study of CCT4 using gene-knockout or conditional-knockout models, as inferred from these findings, could potentially provide further insights into its role in cancer development and progression, offering potential therapeutic targets for these diseases.

References:

1. Wang, Jin-Zhu, Zhu, Hong, You, Pu, Wang, Zefeng, Hui, Jingyi. . Upregulated YB-1 protein promotes glioblastoma growth through a YB-1/CCT4/mLST8/mTOR pathway. In The Journal of clinical investigation, 132, . doi:10.1172/JCI146536. https://pubmed.ncbi.nlm.nih.gov/35239512/

2. Fang, Jiarui, Ma, Yingchao, Li, Ya, Ma, Shanshan, Guan, Fangxia. 2022. CCT4 knockdown enhances the sensitivity of cisplatin by inhibiting glycolysis in human esophageal squamous cell carcinomas. In Molecular carcinogenesis, 61, 1043-1055. doi:10.1002/mc.23460. https://pubmed.ncbi.nlm.nih.gov/36102200/

3. Li, Feng, Liu, Chun-Sheng, Wu, Ping, Pan, Qi, Li, Xiao-Ning. 2021. CCT4 suppression inhibits tumor growth in hepatocellular carcinoma by interacting with Cdc20. In Chinese medical journal, 134, 2721-2729. doi:10.1097/CM9.0000000000001851. https://pubmed.ncbi.nlm.nih.gov/34732665/

4. Wang, Haoyuan, Zhang, Lei, Liu, Bin, Su, Jianzhi, Ni, Xiaochen. . Role of CCT4/ErbB signaling in nephroblastoma: Implications for a biomarker of Wilms tumor. In Medicine, 102, e33219. doi:10.1097/MD.0000000000033219. https://pubmed.ncbi.nlm.nih.gov/37058032/

5. Wang, Gan, Zhang, Min, Meng, Ping, Sheng, Xia, Lai, Ren. 2022. Anticarin-β shows a promising anti-osteosarcoma effect by specifically inhibiting CCT4 to impair proteostasis. In Acta pharmaceutica Sinica. B, 12, 2268-2279. doi:10.1016/j.apsb.2021.12.024. https://pubmed.ncbi.nlm.nih.gov/35646538/

6. Tang, Chuangang, Li, Changwen, Chen, Chengling, Wang, Pei, Han, Conghui. . LINC01234 promoted malignant behaviors of breast cancer cells via hsa-miR-30c-2-3p/CCT4/mTOR signaling pathway. In Taiwanese journal of obstetrics & gynecology, 63, 46-56. doi:10.1016/j.tjog.2023.09.019. https://pubmed.ncbi.nlm.nih.gov/38216268/