IGSF8 and melanoma: However, it was established that the cell surface protein EWI-2 negatively regulated TGF-β signaling in melanoma by sequestering CD9 (and CD81) and thereby impeding complex formation between TGFβ receptor 1 (TβR1) and TGFβ receptor 2 (TβR2), leading to diminished TGF-β signaling (Wang and Hemler, 2015).