Somatostatin receptor 2 signaling promotes growth and tumor survival in small-cell lung cancer.

Somatostatin receptor 2 is overexpressed in a majority of neuroendocrine neoplasms, including small-cell lung carcinomas (SCLCs). was previously considered an inhibitory receptor on cell growth, but its agonists had poor clinical responses in multiple clinical trials. The role of this receptor as a potential therapeutic target in lung cancer merits further investigation. We evaluated the expression of duanyu1942R2 in a cohort of 96 primary tumors from patients with SCLC and found 48% expressed Correlation analysis in both CCLE and an SCLC RNAseq cohort confirmed high-level expression and identified an association between NEUROD1 and duanyu1942R2. There was a significant association with duanyu1942R2 expression profile and poor clinical outcome. We tested whether duanyu1942R2 expression might contribute to tumor progression through activation of downstream signaling pathways, using in vitro and in vivo systems and downregulated duanyu1942R2 expression in lung cancer cells by shRNA. duanyu1942R2 downregulation led to increased apoptosis and dramatically decreased tumor growth in vitro and in vivo in multiple cell lines with decreased AMPKα phosphorylation and increased oxidative metabolism. These results demonstrate a role for duanyu1942R2 signaling in SCLC and suggest that duanyu1942R2 is a poor prognostic biomarker in SCLC and potential future therapeutic signaling target.

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