Tmem209, a transmembrane protein, is involved in multiple biological processes such as substance transportation and signal transduction [1]. It is normally mainly expressed in the testis, but aberrantly expressed in various cancers. In the Wnt/β -catenin signaling pathway, it promotes hepatocellular carcinoma (HCC) progression by stabilizing KPNB1, which in turn activates the pathway, enhancing HCC cell proliferation, migration, invasion, and EMT both in vitro and in vivo [1]. In lung cancer, TMEM209 localizes to the nuclear envelope, Golgi apparatus, and cytoplasm of cancer cells. Overexpression promotes cell growth, while attenuation blocks it. It interacts with NUP205, stabilizing it and increasing nuclear c-Myc levels, driving lung cancer proliferation [2].

A potential key gene related to tubal factor infertility (TFI), TMEM209, was identified through constructing a ceRNA network [3]. In esophageal squamous cell carcinoma (ESCC), TMEM209 was integrated into a prognostic risk-scoring model along with other genes, which can predict overall survival, immune cell infiltration, and response to immunotherapy and chemotherapy [4]. Nucleotide changes in TMEM209 were detected in splenic marginal-zone lymphoma, although its exact role in this disease from these changes is yet to be fully understood [5].

In summary, Tmem209 is crucial in the progression of multiple cancers like HCC and lung cancer, and is also associated with TFI and ESCC prognosis. Functional studies in relevant disease models help elucidate its role in these biological processes and disease conditions, potentially offering new biomarker and therapeutic target opportunities for these diseases [1,2,3,4,5].

References:

1. Fang, Haoran, Shi, Xiaoyi, Gao, Jie, Zhang, Jiacheng, Guo, Wenzhi. 2024. TMEM209 promotes hepatocellular carcinoma progression by activating the Wnt/β-catenin signaling pathway through KPNB1 stabilization. In Cell death discovery, 10, 438. doi:10.1038/s41420-024-02207-9. https://pubmed.ncbi.nlm.nih.gov/39414762/

2. Fujitomo, Takashi, Daigo, Yataro, Matsuda, Koichi, Ueda, Koji, Nakamura, Yusuke. 2012. Critical function for nuclear envelope protein TMEM209 in human pulmonary carcinogenesis. In Cancer research, 72, 4110-8. doi:10.1158/0008-5472.CAN-12-0159. https://pubmed.ncbi.nlm.nih.gov/22719065/

3. Li, Junzui, Ren, Lulu, Li, Meina, Chen, Jiahao, Chen, Qionghua. . Screening of Potential Key Genes Related to Tubal Factor Infertility Based on Competitive Endogenous RNA Network. In Genetic testing and molecular biomarkers, 25, 325-333. doi:10.1089/gtmb.2020.0083. https://pubmed.ncbi.nlm.nih.gov/34003694/

4. Zhang, Xun, Yu, Chuting, Zhou, Siwei, Lin, Han, Wang, Luo-Wei. 2024. Risk model based on genes regulating the response of tumor cells to T-cell-mediated killing in esophageal squamous cell carcinoma. In Aging, 16, 2494-2516. doi:10.18632/aging.205495. https://pubmed.ncbi.nlm.nih.gov/38305770/

5. Fresquet, Vicente, Robles, Eloy F, Parker, Anton, Oscier, David, Martinez-Climent, Jose Angel. 2012. High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma. In British journal of haematology, 158, 712-26. doi:10.1111/j.1365-2141.2012.09226.x. https://pubmed.ncbi.nlm.nih.gov/22816737/