Tspan1, also known as NET-1, TM4C, C4.8 or GEF, is a member of the tetraspanin (TSPAN) family of membrane receptors. TSPANs are involved in various physiological processes, acting as scaffolding proteins for anchoring multiple proteins and in cell signaling. Tspan1 has been implicated in cell survival, proliferation, invasion, and is highly involved in carcinogenesis and chemoresistance [1].

In pancreatic cancer, Tspan1 depletion decreased cell proliferation in vitro and in vivo. It is a positive regulator of autophagy, promoting autophagy maturation via direct binding to LC3. The WNT-CTNNB1 signaling pathway upregulates Tspan1 through FAM83A, and both Tspan1 and FAM83A are targets of MIR454. The MIR454-FAM83A-Tspan1 axis may be valuable prognosis markers or therapeutic targets [2].

In nasopharyngeal carcinoma, Tspan1 inhibited in vitro migration and invasion and in vivo metastasis by interacting with IKBB protein and preventing over-activation of the NF-κB pathway. Reduced Tspan1 expression was associated with metastasis and poor prognosis [3].

In head and neck squamous cell carcinoma, Tspan1 depletion reduced cell proliferation, induced apoptosis, decreased autophagy, sensitized cells to chemotherapeutic agents, and inhibited signaling cascades including phospho-SRC. In vivo, it decreased tumor size, proliferation, and metastatic spreading [4].

In conclusion, Tspan1 plays crucial roles in cancer-related biological processes such as cell proliferation, invasion, autophagy, and chemoresistance. Studies, including those using loss-of-function approaches, have revealed its significance in pancreatic, nasopharyngeal, and head and neck squamous cell carcinomas, providing potential therapeutic targets for these diseases.