Sema3C, also known as Semaphorin 3C, is a secreted protein that plays significant roles in multiple biological processes. It is involved in various signaling pathways such as AKT/Gli1/c-Myc, NF-κB, canonical WNT, and others. Sema3C is important in development, especially in the nervous system where semaphorins are well-known for axon guidance. In the context of disease, it has been linked to cancer progression and fibrosis [1-4].

In liver-related diseases, deletion of Sema3C in activated hepatic stellate cells (HSCs) reduces myofibroblast marker expression and liver fibrosis in mice, indicating its role in exacerbating liver fibrosis [3]. In hepatocellular carcinoma (HCC), blockade of Sema3C effectively inhibits tumor growth and sensitizes HCC cells to sorafenib in vivo, suggesting it promotes HCC progression by reshaping the stromal microenvironment [1]. In glioblastoma, combined depletion of Sema3C and β-catenin partner TCF1 extends animal survival more than single target inhibition alone, showing its role in activating the canonical WNT pathway [2].

In conclusion, Sema3C is a multifunctional protein involved in important biological processes and disease conditions. Gene-knockout or conditional-knockout mouse models have been crucial in revealing its role in liver fibrosis, hepatocellular carcinoma, glioblastoma, and potentially other diseases, providing insights into potential therapeutic targets for these conditions.