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Description

Tetraspanin-8 (UniProt: Q8R3G9, also known as Tspan8, Tspan-8) is encoded by the Tspan8 gene (Gene ID: 216350) in murine species. Tspan-8 is a multi-pass membrane protein of the tetraspanin family that is involved in the regulation of cell activation, growth, and motility. Members of this family have emerged as important regulators of expression levels, trafficking or post-translational modification of laminin-binding integrins. Tetraspanins are shown to associate with one another and cluster dynamically with a large variety of transmembrane and signal-transducing partners, forming specialized membrane microdomains called tetraspanin web. Tspan-8 is reported to be overexpressed during the progression of colorectal, liver, pancreatic and gastric cancers and its increased expression is shown to promote liver and lung metastasis. Overexpression of Tspan-8 has also been correlated with poor prognosis in human colorectal cancer. In metastatic pancreatic and colorectal carcinoma cell lines, PKC activation enhances the colocalization of Tspan-8 and Tspan CD151 with integrin alpha6beta 4 and subsequent internalization of this integrin-tetraspanin complex, resulting in decreased cell-matrix adhesion and increased cell migration. Tspan-8 knockdown in HT29 colon cancer cells is reported to significantly reduce cell migratory ability as a result of an upregulation of both integrin-dependent cell-matrix adhesion and calcium-dependent cell-cell adhesion. (Ref.: Kharbili, ME., et al. (2017). Oncotarget. 8(10), 17140-17155).