We identify Gαs as a novel tumor suppressor in medulloblastoma that functions principally by inhibition of sonic hedgehog signaling. Gαs not only stimulates cyclic adenosine monophosphate (cAMP)-dependent signaling but also inhibits ciliary trafficking of hedgehog components. Elevation of cAMP inhibits medulloblastoma growth and augments inhibition of smoothened to decrease tumor cell proliferation, thus highlighting Gαs as a potential therapeutic target.
Keywords: Cilia; G-protein; GNAS; GPCR; Smoothened; Sonic hedgehog signaling; cAMP; medulloblastoma; pediatric brain tumors; tumor cell origins.