TMEM158, also known as RIS1, is a gene whose function has been increasingly studied in the context of various cancers. It has been implicated in promoting tumor progression through various signaling pathways such as STAT3, PI3K/AKT, and TGF-β [1-4, 6-8, 10]. Genetic models, especially loss-of-function models, can significantly contribute to understanding its role in tumorigenesis.

In gliomas, silencing TMEM158 inhibited cell proliferation, and in vivo results confirmed the inhibitory effect of its down-regulation on glioma growth, suggesting its oncogenic role through STAT3 activation [1]. In lung adenocarcinoma, knockdown of TMEM158 produced opposite effects to its overexpression, which promoted cell proliferation, cell cycle progression, migration, and invasion, via the PI3K/AKT pathway [2]. In triple-negative breast cancer, overexpressed TMEM158 participated in EMT by activating the TGF-β pathway, promoting tumor migration, invasion, and metastasis [3]. Similar oncogenic roles were seen in pancreatic, colorectal, ovarian, and anaplastic thyroid carcinomas [4, 6-8, 10]. In contrast, in prostate cancer, TMEM158 was down-regulated, negatively regulated by AR signaling, and associated with better survival outcomes [4].

In conclusion, TMEM158 generally acts as an oncogene in multiple cancers, promoting processes like cell proliferation, migration, invasion, and drug resistance through various signaling pathways. However, in prostate cancer, it seems to have an opposite role. The study of TMEM158 using gene knockout or conditional knockout models has been crucial in uncovering its role in different cancer types, providing potential therapeutic targets for cancer treatment.

References:

1. Li, Jiabo, Wang, Xuya, Chen, Lulu, Zhang, Chen, Yang, Xuejun. 2022. TMEM158 promotes the proliferation and migration of glioma cells via STAT3 signaling in glioblastomas. In Cancer gene therapy, 29, 1117-1129. doi:10.1038/s41417-021-00414-5. https://pubmed.ncbi.nlm.nih.gov/34992215/

2. Xu, Tao, Yin, Fang, Shi, Kaihu. 2024. TMEM158 functions as an oncogene and promotes lung adenocarcinoma progression through the PI3K/AKT pathway via interaction with TWIST1. In Experimental cell research, 437, 114010. doi:10.1016/j.yexcr.2024.114010. https://pubmed.ncbi.nlm.nih.gov/38508329/

3. Tong, Jiaci, Li, Haoran, Hu, Ye, Zhao, ZuoWei, Li, Man. 2022. TMEM158 Regulates the Canonical and Non-Canonical Pathways of TGF-β to Mediate EMT in Triple-Negative Breast Cancer. In Journal of Cancer, 13, 2694-2704. doi:10.7150/jca.65822. https://pubmed.ncbi.nlm.nih.gov/35711843/

4. Huang, Jian, Liu, Wang, Zhang, Da, Lin, Biyun, Li, Benyi. 2022. TMEM158 expression is negatively regulated by AR signaling and associated with favorite survival outcomes in prostate cancers. In Frontiers in oncology, 12, 1023455. doi:10.3389/fonc.2022.1023455. https://pubmed.ncbi.nlm.nih.gov/36387246/