التفاصيل البيبلوغرافية
| العنوان: |
GPR116, an Adhesion G-Protein--Coupled Receptor, Promotes Breast Cancer Metastasis via the Gαq-p63RhoGEF-Rho GTPase Pathway. |
| المؤلفون: |
Xiaolong Tang1, Rongrong Jin1, Guojun Qu1, Xiu Wang1, Zhenxi Li1, Zengjin Yuan1, Chen Zhao1, Siwko, Stefan2, Tieliu Shi1, Ping Wang1, Jianru Xiao1, Mingyao Liu1,2, Jian Luo1 jluo@bio.ecnu.edu.cn |
| المصدر: |
Cancer Research. Nov2013, Vol. 73 Issue 20, p6206-6218. 13p. |
| مصطلحات موضوعية: |
*G protein coupled receptors, *CELL receptors, *BREAST cancer, *CANCER, *METASTASIS |
| مستخلص: |
Adhesion G-protein-coupled receptors (GPCR), which contain adhesion domains in their extracellular region, have been found to play important roles in cell adhesion, motility, embryonic development, and immune response. Because most adhesion molecules with adhesion domains have vital roles in cancer metastasis, we speculated that adhesion GPCRs are potentially involved in cancer metastasis. In this study, we identified GPR116 as a novel regulator of breast cancer metastasis through expression and functional screening of the adhesion GPCR family. We found that knockdown of GPR116 in highly metastatic (MDA-MB-231) breast cancer cells suppressed cell migration and invasion. Conversely, ectopic GPR116 expression in poorly metastatic (MCF-7 and Hs578T) cells promoted cell invasion. We further showed that knockdown of GPR116 inhibited breast cancer cell metastasis in two mammary tumor metastasis mouse models. Moreover, GPR116 modulated the formation of lamellipodia and actin stress fibers in cells in a RhoA- and Rac1-dependent manner. At a molecular level, GPR116 regulated cell motility and morphology through the Gαq-p63RhoGEF-RhoA/Rac1 pathway. The biologic significance of GPR116 in breast cancer is substantiated in human patient samples, where GPR116 expression is significantly correlated with breast tumor progression, recurrence, and poor prognosis. These findings show that GPR116 is crucial for the metastasis of breast cancer and support GPR116 as a potential prognostic marker and drug target against metastatic human breast cancer. [ABSTRACT FROM AUTHOR] |
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