Igsf9-KO Mouse

IgSF9, also known as immunoglobulin superfamily member 9 or Dasm1, belongs to an evolutionarily ancient protein family. Proteins in this family are expressed in the nervous system and have functions similar to neural cell adhesion molecule family proteins, facilitating homophilic cell adhesion, neurite outgrowth and branching, axon guidance, synapse maturation, self-avoidance, and tiling [1]. In addition, they are involved in several disease-related pathways, such as those related to cancer and liver diseases.

In cancer research, IgSF9 has been found to have different roles. In lung cancer, it promotes tumor invasion and metastasis through the GSK-3β/β-catenin mediated epithelial-to-mesenchymal transition (EMT) pathway [2]. In breast cancer, wild-type p53 trans-activates IgSF9, which then inhibits breast cancer metastasis by interacting with focal adhesion kinase (FAK) and inhibiting the FAK/AKT signaling activity [4]. Low expression of IgSF9 is associated with lymphatic vessel invasion, lymph node metastasis, and advanced TNM staging in breast cancer, making it a potential prognostic marker and therapeutic target [5,7]. In endometrial cancer, IgSF9 is overexpressed, and its expression is associated with myometrium invasion and poor prognosis, suggesting it as a new biomarker [9]. Also, in nasopharyngeal carcinoma, IgSF9 is related to prognosis and hypoxia, with down-regulated IgSF9 reducing cell proliferation, migration, and invasion ability [6]. In terms of its role in the immune system, IgSF9 is an immune checkpoint regulator that suppresses T-cell activation in cancer. Anti-IgSF9 antibody treatment can inhibit tumor growth and enhance the efficacy of anti-programmed cell death protein 1 immunotherapy [3]. Additionally, IgSF9 is among the top differentially expressed proteins associated with both liver steatosis and fibrosis in people living with HIV [8].

In conclusion, IgSF9 plays crucial roles in both neural development-related biological processes and multiple disease conditions, especially in various cancers and liver diseases. Studies on IgSF9 using different research models, including those involving loss-of-function experiments, have provided valuable insights into its functions and potential as a biomarker or therapeutic target in these disease areas.