Cell surface transmembrane protein IGFS8 (herein called EWI-2) negatively regulates melanoma TGF-β signaling and is well positioned to control the transition in TGF-β signaling from cytostatic (in early melanoma stages) to pro-invasion/metastasis (in later stages). EWI-2 functions by sequestering the tetraspanin proteins CD9 and CD81, thereby making them unavailable to support the association of TGFβ receptor 1 with TGFβ receptor 2.
Keywords: CD81; CD9; EWI-2/IGSF8; TGF-β1; melanoma; tetraspanins.