CMKLR1/PKA signaling reinforces sonic hedgehog pathway to promote medulloblastoma pathogenesis.

ABSTRACT: Aberrant Hedgehog signaling is a key driver of malignancies like medulloblastoma (MB), the most common pediatric brain tumor originating from cerebellar granule neuron progenitors with largely uncharacterized mechanisms. We found here that the G protein-coupled receptor, chemokine-like receptor 1 (CMKLR1), is upregulated and correlates with the development of Sonic Hedgehog (SHH)-subtype MB. SHH and the downstream transcription factor Gli2 license the expression of CMKLR1, which promotes the growth and migration of cells by activating Gα(i)βγ and subsequently the PI3K/Akt signal pathway. SHH/Gli also transcriptionally represses Regulator of G Protein Signaling 16 (RGS16), a known suppressor of Gα(i). Meanwhile, CMKLR1/Gα(i) signaling inactivates protein kinase A (PKA), reduces PKA-catalyze

SUBMITTER: Wang S 

PROVIDER: S-EPMC12624127 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature