Cross talk between the bombesin neuropeptide receptor and Sonic hedgehog pathways in small cell lung carcinoma.

ABSTRACT: Small cell lung carcinoma (SCLC) often features the upregulation of the Sonic hedgehog (Shh) pathway leading to activation of Gli transcription factors. SCLC cells secrete bombesin (BBS)-like neuropeptides that act as autocrine growth factors. Here, we show that SCLC tumor samples feature co-expression of Shh and BBS-cognate receptor (gastrin-releasing peptide receptor (GRPR)). We also demonstrate that BBS activates Gli in SCLC cells, which is crucial for BBS-mediated SCLC proliferation, because cyclopamine, an inhibitor of the Shh pathway, hampered the BBS-mediated effects. BBS binding to GRPR stimulated Gli through its downstream Gαq and Gα₁₂/₁₃ GTPases, and consistently, other Gαq and Gα₁₃ coupled receptors (such as muscarinic receptor, m1, and thrombin receptor, PAR-1) and constitutive

SUBMITTER: Castellone MD 

PROVIDER: S-EPMC4539617 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature