TM4SF4, a member of the transmembrane 4 superfamily, has physiological functions in regulating tissue differentiation, signal transduction, cellular activation, proliferation, motility, adhesion, and angiogenesis [4]. It is involved in multiple pathways such as the AKT, IGF1-IGF1R, and STAT3 pathways [1,5,7]. Its abnormal expression is associated with the development of various cancers, making it a potential biomarker and therapeutic target.

In papillary thyroid cancer (PTC), TM4SF4 is significantly upregulated and serves as a diagnostic biomarker. Downregulation of TM4SF4 suppresses the proliferation and metastasis of PTC cell lines while inducing apoptosis, and the AKT activator can reverse these effects, suggesting it promotes PTC progression via the AKT pathway [1]. In lung and breast cancers, TM4SF4 was identified as a potential therapeutic target through outlier analysis, and its knockdown suppressed the growth of cancer cell lines [2]. In hepatocellular carcinoma, the lncRNA ST8SIA6-AS1 promotes cancer progression by regulating the miR-651-5p/TM4SF4 axis [3]. In radiation-resistant lung adenocarcinoma cells, TM4SF4 overexpression activates IGF1R via elevation of IGF1, leading to resistance to radiotherapy [5]. In colorectal cancer, the TYMS-TM4SF4 axis promotes cancer progression through EMT and upregulating stem cell markers [6].

In conclusion, TM4SF4 is a key molecule involved in the progression of multiple cancers, playing important roles in cell proliferation, metastasis, and resistance to treatment. Its study in various cancer models provides insights into the disease mechanisms, highlighting its potential as a biomarker and therapeutic target for cancers such as PTC, lung, breast, hepatocellular, and colorectal cancers.

References:

1. Lin, Lizhi, Wen, Jialiang, Xu, Tiansheng, Si, Yuhao. 2024. TM4SF4 is a diagnostic biomarker accelerating progression of papillary thyroid cancer via AKT pathway. In Cancer biology & therapy, 25, 2424570. doi:10.1080/15384047.2024.2424570. https://pubmed.ncbi.nlm.nih.gov/39497261/

2. Jung, Kyungsoo, Choi, Joon-Seok, Koo, Beom-Mo, Oh, Doo-Yi, Choi, Yoon-La. 2020. TM4SF4 and LRRK2 Are Potential Therapeutic Targets in Lung and Breast Cancers through Outlier Analysis. In Cancer research and treatment, 53, 9-24. doi:10.4143/crt.2020.434. https://pubmed.ncbi.nlm.nih.gov/32972043/

3. Mou, Yanjie, Ding, Xiaoming. 2022. LncRNA ST8SIA6-AS1 facilitates hepatocellular carcinoma progression by governing miR-651-5p/TM4SF4 axis. In Anti-cancer drugs, 33, 741-751. doi:10.1097/CAD.0000000000001326. https://pubmed.ncbi.nlm.nih.gov/35946523/

4. Rahim, Nur Syafiqah, Wu, Yuan Seng, Sim, Maw Shin, Sekar, Mahendran, Guad, Rhanye Mac. 2023. Three Members of Transmembrane-4-Superfamily, TM4SF1, TM4SF4, and TM4SF5, as Emerging Anticancer Molecular Targets against Cancer Phenotypes and Chemoresistance. In Pharmaceuticals (Basel, Switzerland), 16, . doi:10.3390/ph16010110. https://pubmed.ncbi.nlm.nih.gov/36678607/

5. Choi, Soo-Im, Kim, Seo-Yeon, Lee, Jaeha, Cho, Eun-Wie, Kim, In-Gyu. . TM4SF4 overexpression in radiation-resistant lung carcinoma cells activates IGF1R via elevation of IGF1. In Oncotarget, 5, 9823-37. doi:. https://pubmed.ncbi.nlm.nih.gov/25344917/

6. Zhang, Fen, Ye, Jiecheng, Guo, Wenjing, Wang, Liyuan, Han, Anjia. 2022. TYMS-TM4SF4 axis promotes the progression of colorectal cancer by EMT and upregulating stem cell marker. In American journal of cancer research, 12, 1009-1026. doi:. https://pubmed.ncbi.nlm.nih.gov/35411242/

7. Choi, Soo Im, Kim, Seo Yoen, Lee, Jei Ha, Cho, Eun Wie, Kim, In-Gyu. 2017. Osteopontin production by TM4SF4 signaling drives a positive feedback autocrine loop with the STAT3 pathway to maintain cancer stem cell-like properties in lung cancer cells. In Oncotarget, 8, 101284-101297. doi:10.18632/oncotarget.21021. https://pubmed.ncbi.nlm.nih.gov/29254164/