Tetraspanin-6 (TSPAN6)

Tetraspanin-6 is a glycosylated, small integral membrane protein found on the cell surface, encoded by the human TSPAN6 gene. It possesses four highly hydrophobic and conserved transmembrane domains (TM1–TM4), interconnected by one small and one large extracellular loop (EC1 and EC2), with short N- and C-terminal cytoplasmic tails. Tetraspanin-6 acts as a molecular scaffold organizing protein networks in membrane microdomains, facilitating interactions between cell surface receptors, integrins, and signaling molecules. It participates in numerous cellular processes, including cell proliferation, adhesion, migration, signaling, and membrane compartmentalization. Tetraspanin-6’s decreased expression is associated with poor prognosis in colorectal cancer and correlates with reduced sensitivity to EGFR-targeted therapies. It is beginning to be appreciated as a tumor suppressor and predictive biomarker for Cetuximab therapy in colorectal cancer.

Other names

TSPAN6Transmembrane 4 superfamily member 6TM4SF6

Modulation of EGFR-based signaling by regulating secretion and distribution of TGF-α (tumor suppressor function); Acts via protein complex formation with syntenin-1 and transmembrane TGF-α