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.
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.
复制标题
DOI：
10.3892/ijo.2012.1379
复制
发表时间：
2012-05
影响因子：
5.2
通讯作者：
Lee MJ
中科院分区：
文献类型：
--
作者：
Hsu A;Zhang W;Lee JF;An J;Ekambaram P;Liu J;Honn KV;Klinge CM;Lee MJ
鞘氨醇-1-磷酸（S1 P）调节广泛的生物学功能。然而，S1 P信号在肿瘤发生中的作用仍有待阐明。在这项研究中，我们发现，S1 P受体亚型3（S1 P3）是显着上调，在一个亚组的肺腺癌细胞相比，正常肺上皮细胞。特异性敲低S1 P3受体抑制肺腺癌细胞增殖和非贴壁依赖性生长从机制上讲，我们证明了S1 P3信号通过Rho激酶（ROCK）途径在肺腺癌细胞中增加表皮生长因子受体（EGFR）的表达。核径流分析表明，S1 P/S1 P3信号转导转录增加EGFR表达。S1 P3受体的敲除减少了肺腺癌细胞中S1 P刺激的EGFR表达。此外，S1 P处理显著增强EGF刺激的肺腺癌细胞集落形成、增殖和侵袭。总之，这些结果表明，增强的S1 P3-EGFR信号传导轴可能有助于肺腺癌的肿瘤发生或进展。
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.
登录
查看更多内容
影响因子：
2.3
作者：
Estrada, Rosendo;Wang, Lichun;Jala, Venkatakrishna R.;Lee, Jen-Fu;Lin, Cheng-Yon;Gray, Robert D.;Haribabu, Bodduluri;Lee, Menq-Jer
通讯作者：
Lee, Menq-Jer
影响因子：
4.1
作者：
Ivanova MM;Mazhawidza W;Dougherty SM;Minna JD;Klinge CM
通讯作者：
Klinge CM
DOI：
10.1152/ajpheart.00097.2008
发表时间：
2009-01-01
影响因子：
4.8
作者：
Lee, Jen-Fu;Gordon, Sharon;Lee, Menq-Jer
通讯作者：
Lee, Menq-Jer
影响因子：
56.9
作者：
Lee, MJ;Van Brocklyn, JR;Hla, T
通讯作者：
Hla, T
影响因子：
8
作者：
Gazdar, A. F.
通讯作者：
Gazdar, A. F.