TMEM106A, a type II transmembrane protein, has diverse essential functions. It is involved in the host defense against enveloped viruses by inhibiting their release from the cell surface [1]. In cancer, it often acts as a tumor suppressor, affecting processes like cell proliferation, migration, invasion, and apoptosis in various cancer types [2,3,4,8]. It also plays a role in macrophage-related immune responses, regulating macrophage activation and polarization, and is associated with inflammation-related signaling pathways such as MAPK and NF-κB [5,7]. Genetic models, especially knockout models, are valuable for studying its functions.

Tmem106a knockout mice were more sensitive to lipopolysaccharide-induced septic shock, with enhanced macrophage activation and polarization towards the M1 inflammatory phenotype, indicating its role in maintaining macrophage homeostasis [5]. In addition, overexpression of TMEM106A in cancer cell lines led to decreased cell proliferation, migration, and invasion, and increased apoptosis, suggesting its tumor-suppressive role [2,3,4]. Promoter methylation-mediated down-regulation of TMEM106A was observed in hepatocellular carcinoma, colorectal cancer, and gastric cancer, affecting cancer metastasis and patient prognosis [2,6,8].

In conclusion, TMEM106A has important functions in antiviral defense, cancer development, and macrophage-related immune responses. Gene knockout mouse models have been crucial in revealing its role in these processes, especially in understanding the mechanisms of septic shock and cancer progression, providing potential therapeutic targets for these diseases.

References:

1. Mao, Dexin, Yan, Feixiang, Zhang, Xiaolin, Gao, Guangxia. 2022. TMEM106A inhibits enveloped virus release from cell surface. In iScience, 25, 103843. doi:10.1016/j.isci.2022.103843. https://pubmed.ncbi.nlm.nih.gov/35198896/

2. Shi, Shiming, Wang, Biao, Wan, Jinglei, Yu, Lei, Dai, Zhi. . TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma. In Acta biochimica et biophysica Sinica, 54, 1008-1020. doi:10.3724/abbs.2022069. https://pubmed.ncbi.nlm.nih.gov/35713314/

3. Liu, Juncai, Zhu, Hongjing. 2018. TMEM106A inhibits cell proliferation, migration, and induces apoptosis of lung cancer cells. In Journal of cellular biochemistry, 120, 7825-7833. doi:10.1002/jcb.28057. https://pubmed.ncbi.nlm.nih.gov/30456879/

4. Wu, Chenglong, Xu, Juan, Wang, Han, Li, Xuyi, Tang, Aifa. 2017. TMEM106a is a Novel Tumor Suppressor in Human Renal Cancer. In Kidney & blood pressure research, 42, 853-864. doi:10.1159/000484495. https://pubmed.ncbi.nlm.nih.gov/29131025/

5. Zhang, X, Feng, T, Zhou, X, Liu, H, Chen, Y. 2020. Inactivation of TMEM106A promotes lipopolysaccharide-induced inflammation via the MAPK and NF-κB signaling pathways in macrophages. In Clinical and experimental immunology, 203, 125-136. doi:10.1111/cei.13528. https://pubmed.ncbi.nlm.nih.gov/33006758/

6. Liu, Zaoqu, Weng, Siyuan, Dang, Qin, Sun, Zhenqiang, Han, Xinwei. 2022. Gene interaction perturbation network deciphers a high-resolution taxonomy in colorectal cancer. In eLife, 11, . doi:10.7554/eLife.81114. https://pubmed.ncbi.nlm.nih.gov/36345721/

7. Dai, Hui, Xu, Dong, Su, Jing, Jang, Jingyuan, Chen, Yingyu. 2015. Transmembrane protein 106a activates mouse peritoneal macrophages via the MAPK and NF-κB signaling pathways. In Scientific reports, 5, 12461. doi:10.1038/srep12461. https://pubmed.ncbi.nlm.nih.gov/26215746/

8. Xu, Dong, Qu, Liujing, Hu, Jia, Guo, Mingzhou, Chen, Yingyu. 2014. Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis. In Journal of cellular and molecular medicine, 18, 1655-66. doi:10.1111/jcmm.12352. https://pubmed.ncbi.nlm.nih.gov/24975047/