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

Publication ,  Journal Article
Lehman, JM; Hoeksema, MD; Staub, J; Qian, J; Harris, B; Callison, JC; Miao, J; Shi, C; Eisenberg, R; Chen, H; Chen, S-C; Massion, PP
Published in: Int J Cancer
March 1, 2019

Somatostatin receptor 2 (SSTR2) is overexpressed in a majority of neuroendocrine neoplasms, including small-cell lung carcinomas (SCLCs). SSTR2 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 SSTR2 in a cohort of 96 primary tumors from patients with SCLC and found 48% expressed SSTR2. Correlation analysis in both CCLE and an SCLC RNAseq cohort confirmed high-level expression and identified an association between NEUROD1 and SSTR2. There was a significant association with SSTR2 expression profile and poor clinical outcome. We tested whether SSTR2 expression might contribute to tumor progression through activation of downstream signaling pathways, using in vitro and in vivo systems and downregulated SSTR2 expression in lung cancer cells by shRNA. SSTR2 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 SSTR2 signaling in SCLC and suggest that SSTR2 is a poor prognostic biomarker in SCLC and potential future therapeutic signaling target.

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

March 1, 2019

Volume

144

Issue

5

Start / End Page

1104 / 1114

Location

United States

Related Subject Headings

  • Small Cell Lung Carcinoma
  • Signal Transduction
  • Receptors, Somatostatin
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Nerve Tissue Proteins
  • Mice, Nude
  • Mice
  • Lung Neoplasms
  • Humans
 

Citation

APA
Chicago
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MLA
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Lehman, J. M., Hoeksema, M. D., Staub, J., Qian, J., Harris, B., Callison, J. C., … Massion, P. P. (2019). Somatostatin receptor 2 signaling promotes growth and tumor survival in small-cell lung cancer. Int J Cancer, 144(5), 1104–1114. https://doi.org/10.1002/ijc.31771
Lehman, Jonathan M., Megan D. Hoeksema, Jeremy Staub, Jun Qian, Bradford Harris, J Clay Callison, Jennifer Miao, et al. “Somatostatin receptor 2 signaling promotes growth and tumor survival in small-cell lung cancer.Int J Cancer 144, no. 5 (March 1, 2019): 1104–14. https://doi.org/10.1002/ijc.31771.
Lehman JM, Hoeksema MD, Staub J, Qian J, Harris B, Callison JC, et al. Somatostatin receptor 2 signaling promotes growth and tumor survival in small-cell lung cancer. Int J Cancer. 2019 Mar 1;144(5):1104–14.
Lehman, Jonathan M., et al. “Somatostatin receptor 2 signaling promotes growth and tumor survival in small-cell lung cancer.Int J Cancer, vol. 144, no. 5, Mar. 2019, pp. 1104–14. Pubmed, doi:10.1002/ijc.31771.
Lehman JM, Hoeksema MD, Staub J, Qian J, Harris B, Callison JC, Miao J, Shi C, Eisenberg R, Chen H, Chen S-C, Massion PP. Somatostatin receptor 2 signaling promotes growth and tumor survival in small-cell lung cancer. Int J Cancer. 2019 Mar 1;144(5):1104–1114.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

March 1, 2019

Volume

144

Issue

5

Start / End Page

1104 / 1114

Location

United States

Related Subject Headings

  • Small Cell Lung Carcinoma
  • Signal Transduction
  • Receptors, Somatostatin
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Nerve Tissue Proteins
  • Mice, Nude
  • Mice
  • Lung Neoplasms
  • Humans