Sphingosine-1-phosphate receptor-3 signaling up-regulates epidermal growth factor receptor and enhances epidermal growth factor receptor-mediated carcinogenic activities in cultured lung adenocarcinoma cells

  • Authors:
    • Andrew Hsu
    • Wenliang Zhang
    • Jen-Fu Lee
    • Jin An
    • Prasanna Ekambaram
    • Jingjing Liu
    • Kenneth V. Honn
    • Carolyn M. Klinge
    • Menq-Jer Lee
  • View Affiliations

  • Published online on: February 16, 2012     https://doi.org/10.3892/ijo.2012.1379
  • Pages: 1619-1626
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Sphingosine-1-phosphate (S1P) regulates a wide array of biological functions. However, the role of S1P signaling in tumorigenesis remains to be elucidated. In this study, we show that S1P receptor subtype 3 (S1P3) is markedly up-regulated in a subset of lung adenocarcinoma cells compared to normal lung epithelial cells. Specific knockdown of S1P3 receptors inhibits proliferation and anchorage-independent growth of lung adenocarcinoma cells. Mechanistically, we demonstrate that S1P3 signaling increases epidermal growth factor receptor (EGFR) expression via the Rho kinase (ROCK) pathway in lung adenocarcinoma cells. Nuclear run-off analysis indicates that S1P/S1P3 signaling transcriptionally increases EGFR expression. Knockdown of S1P3 receptors diminishes the S1P-stimulated EGFR expression in lung adenocarcinoma cells. Moreover, S1P treatment greatly enhances EGF-stimulated colony formation, proliferation and invasion of lung adenocarcinoma cells. Together, these results suggest that the enhanced S1P3-EGFR signaling axis may contribute to the tumorigenesis or progression of lung adenocarcinomas.

Related Articles

Journal Cover

May 2012
Volume 40 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Hsu A, Zhang W, Lee J, An J, Ekambaram P, Liu J, Honn KV, Klinge CM and Lee M: Sphingosine-1-phosphate receptor-3 signaling up-regulates epidermal growth factor receptor and enhances epidermal growth factor receptor-mediated carcinogenic activities in cultured lung adenocarcinoma cells. Int J Oncol 40: 1619-1626, 2012.
APA
Hsu, A., Zhang, W., Lee, J., An, J., Ekambaram, P., Liu, J. ... Lee, M. (2012). Sphingosine-1-phosphate receptor-3 signaling up-regulates epidermal growth factor receptor and enhances epidermal growth factor receptor-mediated carcinogenic activities in cultured lung adenocarcinoma cells. International Journal of Oncology, 40, 1619-1626. https://doi.org/10.3892/ijo.2012.1379
MLA
Hsu, A., Zhang, W., Lee, J., An, J., Ekambaram, P., Liu, J., Honn, K. V., Klinge, C. M., Lee, M."Sphingosine-1-phosphate receptor-3 signaling up-regulates epidermal growth factor receptor and enhances epidermal growth factor receptor-mediated carcinogenic activities in cultured lung adenocarcinoma cells". International Journal of Oncology 40.5 (2012): 1619-1626.
Chicago
Hsu, A., Zhang, W., Lee, J., An, J., Ekambaram, P., Liu, J., Honn, K. V., Klinge, C. M., Lee, M."Sphingosine-1-phosphate receptor-3 signaling up-regulates epidermal growth factor receptor and enhances epidermal growth factor receptor-mediated carcinogenic activities in cultured lung adenocarcinoma cells". International Journal of Oncology 40, no. 5 (2012): 1619-1626. https://doi.org/10.3892/ijo.2012.1379