TNS4, also known as Tensin4 or Cten, is a putative oncogene with roles in regulating cell adhesion, motility, invasion, and epithelial to mesenchymal transition (EMT) [2,3]. It is involved in multiple signaling pathways, such as the Wnt, JAK2-STAT3, and EGFR signaling pathways, and plays a significant role in tumor-related biological processes [1,2,4]. Genetic models, like the ApcMin/+ mouse, are valuable for studying TNS4 [2].

In ApcMin/+ mice, TNS4 was upregulated in intestinal adenomas by Wnt signaling, with 91.2% of polyps showing positive TNS4 expression [2]. In gallbladder cancer, knocking down GPRC5A led to down-regulation of TNS4 through the JAK2-STAT3 axis, and GPRC5A promoted cancer metastasis by upregulating TNS4 [1]. In 3D spheroid models of colorectal cancer, TNS4 knockdown increased cell proliferation, reduced adhesiveness and 3D invasion, and enhanced sensitivity to the EGFR inhibitor gefitinib [3].

In conclusion, TNS4 is crucial in regulating cell behaviors related to tumorigenesis. Studies using gene-modified mouse models, like the ApcMin/+ mouse, have revealed its role in promoting the development of intestinal adenomas and other tumor-related processes, highlighting its potential as a therapeutic target in cancer treatment.

References:

1. Yang, Jiahua, Li, Xuechuan, Chen, Shili, Geng, Yajun, Liu, Yingbin. 2024. GPRC5A promotes gallbladder cancer metastasis by upregulating TNS4 via the JAK2-STAT3 pathway. In Cancer letters, 598, 217067. doi:10.1016/j.canlet.2024.217067. https://pubmed.ncbi.nlm.nih.gov/38942137/

2. Raposo, Teresa P, Alfahed, Abdulaziz, Nateri, Abdolrahman S, Ilyas, Mohammad. 2020. Tensin4 (TNS4) is upregulated by Wnt signalling in adenomas in multiple intestinal neoplasia (Min) mice. In International journal of experimental pathology, 101, 80-86. doi:10.1111/iep.12352. https://pubmed.ncbi.nlm.nih.gov/32567731/

3. Raposo, Teresa P, Susanti, Susanti, Ilyas, Mohammad. 2020. Investigating TNS4 in the Colorectal Tumor Microenvironment Using 3D Spheroid Models of Invasion. In Advanced biosystems, 4, e2000031. doi:10.1002/adbi.202000031. https://pubmed.ncbi.nlm.nih.gov/32390347/

4. Yao, Bing, Gui, Tao, Zeng, Xiangwei, Ju, Junyi, Zhao, Quan. 2021. PRMT1-mediated H4R3me2a recruits SMARCA4 to promote colorectal cancer progression by enhancing EGFR signaling. In Genome medicine, 13, 58. doi:10.1186/s13073-021-00871-5. https://pubmed.ncbi.nlm.nih.gov/33853662/