IgSF9, also known as immunoglobulin superfamily member 9 or Dasm1, is a member of an evolutionarily ancient protein family. Proteins in this family generally have a structure similar to neural cell adhesion molecules and are expressed in the nervous system. They have been implicated in functions like neurite outgrowth, axon guidance, synapse maturation, self-avoidance, and tiling [1].

In cancer research, IgSF9 shows diverse roles. In lung cancer, full-length IgSF9 and its intracellular domain (but not extracellular domain) can promote tumor invasion and metastasis through GSK-3β/β-catenin mediated epithelial-to-mesenchymal transition (EMT) [2]. In breast cancer, wild-type p53 trans-activates IgSF9, which then inhibits metastasis by interacting with focal adhesion kinase (FAK) and inhibiting the FAK/AKT signaling activity. Low IgSF9 expression is associated with lymph node metastasis and poor prognosis in invasive micropapillary carcinoma of the breast [3,4]. In nasopharyngeal carcinoma, IgSF9 is related to prognosis and hypoxia, with down-regulated IgSF9 reducing cell proliferation, migration, and invasion ability [5]. In endometrial cancer, IgSF9 is overexpressed, and its expression is associated with myometrium invasion and poor prognosis [6]. Also, in liver diseases of people living with HIV, IgSF9 is among the differentially expressed proteins associated with liver steatosis and fibrosis [7]. In Drosophila, the IgSF9-family protein Borderless regulates axonal transport of synaptic-vesicle components and color vision [8].

In conclusion, IgSF9 is a multifunctional protein with important roles in nervous system development and various disease conditions, especially in cancer metastasis and liver diseases. Research on IgSF9 using different genetic models has provided insights into its functions, helping to understand the biological processes and disease mechanisms, which may offer potential targets for therapeutic intervention.

References:

1. Hansen, Maria, Walmod, Peter Schledermann. 2013. IGSF9 family proteins. In Neurochemical research, 38, 1236-51. doi:10.1007/s11064-013-0999-y. https://pubmed.ncbi.nlm.nih.gov/23417431/

2. Luan, Huiwen, Wang, Ting, Li, Fangmin, Wang, Yaopeng, Li, Zunling. 2024. IGSF9 promotes tumor invasion and metastasis through GSK-3β/β-catenin mediated EMT in lung cancer. In Neoplasia (New York, N.Y.), 58, 101067. doi:10.1016/j.neo.2024.101067. https://pubmed.ncbi.nlm.nih.gov/39383800/

3. Li, Yaohua, Deng, Yiran, Zhao, Yannan, Xu, Yingying, Chen, She. 2022. Immunoglobulin superfamily 9 (IGSF9) is trans-activated by p53, inhibits breast cancer metastasis via FAK. In Oncogene, 41, 4658-4672. doi:10.1038/s41388-022-02459-8. https://pubmed.ncbi.nlm.nih.gov/36088502/

4. Shi, Qianqian, Shao, Kang, Jia, Hongqin, Li, Guibo, Fu, Li. 2022. Genomic alterations and evolution of cell clusters in metastatic invasive micropapillary carcinoma of the breast. In Nature communications, 13, 111. doi:10.1038/s41467-021-27794-4. https://pubmed.ncbi.nlm.nih.gov/35013309/

5. Huang, Donglan, Liu, Qianqian, Zhang, Weijun, Yuan, Yawei, Deng, Min. 2020. Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis. In Cancer cell international, 20, 498. doi:10.1186/s12935-020-01587-z. https://pubmed.ncbi.nlm.nih.gov/33061850/

6. Shaw, Hunter S, Cameron, Scott A, Chang, Wen-Tzu, Rao, Yong. 2019. The Conserved IgSF9 Protein Borderless Regulates Axonal Transport of Presynaptic Components and Color Vision in Drosophila. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 39, 6817-6828. doi:10.1523/JNEUROSCI.0075-19.2019. https://pubmed.ncbi.nlm.nih.gov/31235647/

7. van Eekeren, Louise E, de Mast, Quirijn, Meeder, Elise M G, Tjwa, Eric T T L, Joosten, Leo A B. 2024. Plasma proteomic signatures of liver steatosis and fibrosis in people living with HIV: a cross-sectional study. In EBioMedicine, 109, 105407. doi:10.1016/j.ebiom.2024.105407. https://pubmed.ncbi.nlm.nih.gov/39426127/

8. Shi, Zonggao, Li, Chunyan, Tarwater, Laura, Chandrashekar, Darshan S, Stack, M Sharon. 2018. RNA-seq Reveals the Overexpression of IGSF9 in Endometrial Cancer. In Journal of oncology, 2018, 2439527. doi:10.1155/2018/2439527. https://pubmed.ncbi.nlm.nih.gov/29666643/