Tmc5, or Transmembrane Channel-Like 5, is a protein-coding gene. Homology and AlphaFold2 models suggest it may have a putative ion permeation pathway, potentially acting as an ion channel and lipid scramblase at microvillar tips in intestinal epithelial cells [5]. It is also involved in multiple cancer-related pathways, such as PI3K/AKT, RAS/MAPK, and TSC/mTOR [1].

In cancer research, Tmc5 has been found to be highly expressed in most cancer types compared to normal tissues. In prostate cancer, Tmc5 promotes cell proliferation by regulating the cell cycle, and its knockdown enhances sensitivity to 5-Fluorouracil [2]. In pancreatic adenocarcinoma, Tmc5 is up-regulated in cancerous epithelial cells and more advanced tumor stages, and may be regulated by STAT3 [3]. In hepatocellular carcinoma, it drives cancer progression through epithelial-mesenchymal transition, and is a potential biomarker for tumor-associated telocytes [4,6]. Tmc5 also shows significance in renal clear cell carcinoma prognosis and immune infiltration, and may be a biomarker for colorectal cancer [7,8].

In conclusion, Tmc5 is potentially involved in ion-related functions at microvilli and significantly impacts cancer-related biological processes. Its high expression in various cancers and association with prognosis and drug responses make it a potential biomarker and therapeutic target. Studies on Tmc5 enhance our understanding of cancer mechanisms, offering new perspectives for cancer treatment.

References:

1. Zhang, Hui, Zhang, Xu, Xu, Weiguo, Wang, Jian. 2022. TMC5 is Highly Expressed in Human Cancers and Corelates to Prognosis and Immune Cell Infiltration: A Comprehensive Bioinformatics Analysis. In Frontiers in molecular biosciences, 8, 810864. doi:10.3389/fmolb.2021.810864. https://pubmed.ncbi.nlm.nih.gov/35096973/

2. Zhang, Wanfeng, Wang, Sen, Zhang, Xianqin, Luo, Ruihan, Ran, Longke. 2019. Transmembrane Channel-Like 5 (TMC5) promotes prostate cancer cell proliferation through cell cycle regulation. In Biochimie, 165, 115-122. doi:10.1016/j.biochi.2019.07.017. https://pubmed.ncbi.nlm.nih.gov/31356847/

3. Gan, Xiang-Yu, Li, Jian-Di, Chen, Gang, Li, Jian-Jun, Wei, Dan-Ming. 2022. Role of Up-Regulated Transmembrane Channel-Like Protein 5 in Pancreatic Adenocarcinoma. In Digestive diseases and sciences, 68, 1894-1912. doi:10.1007/s10620-022-07771-7. https://pubmed.ncbi.nlm.nih.gov/36459296/

4. Xu, Ying, Yu, Jing. . TMC5 as a Marker of Tumor-Associated Telocytes in Hepatocellular Carcinoma. In Frontiers in bioscience (Landmark edition), 30, 36583. doi:10.31083/FBL36583. https://pubmed.ncbi.nlm.nih.gov/40302342/

5. Ebrahim, Seham, Ballesteros, Angela, Zheng, W Sharon, Sotomayor, Marcos, Kachar, Bechara. 2024. Transmembrane channel-like 4 and 5 proteins at microvillar tips are potential ion channels and lipid scramblases. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.08.22.609173. https://pubmed.ncbi.nlm.nih.gov/39229161/

6. Li, Jiao, Wang, Zi-Yu, Jin, Yan, Li, Xi, Wang, Xi. . Transmembrane channel-like 5 drives hepatocellular carcinoma progression by regulating epithelial-mesenchymal transition. In World journal of clinical oncology, 16, 94091. doi:10.5306/wjco.v16.i3.94091. https://pubmed.ncbi.nlm.nih.gov/40130046/

7. Tang, Wenbin, Shi, Zhiyuan, Zhu, Yasheng, Xu, Weidong, Wang, Junkai. 2023. Comprehensive analysis of the prognosis and immune infiltration of TMC family members in renal clear cell carcinoma. In Scientific reports, 13, 11668. doi:10.1038/s41598-023-38914-z. https://pubmed.ncbi.nlm.nih.gov/37468683/

8. Zhu, Huifang, Li, Yongzhen, Guo, Jingyu, Qian, Xinlai, He, Guoyang. 2022. Integrated proteomic and phosphoproteomic analysis for characterization of colorectal cancer. In Journal of proteomics, 274, 104808. doi:10.1016/j.jprot.2022.104808. https://pubmed.ncbi.nlm.nih.gov/36596410/