GPR116, an adhesion G-protein-coupled receptor, promotes breast cancer metastasis via the Gαq-p63 Rho GEF-Rho GTPase pathway | Academic Article individual record

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-MB231) 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-p63 Rho GEF-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. © 2013 AACR.

author list (cited authors)
Tang, X., Jin, R., Qu, G., Wang, X., Li, Z., Yuan, Z., ... Luo, J.
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  • Animals
  • Amino Acid Sequence
  • Signal Transduction
  • Mice
  • Neoplasm Metastasis
  • Tissue Array Analysis
  • Cell Line, Tumor
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Cell Adhesion
  • Breast Neoplasms
  • Humans
  • Cell Movement
  • Female
  • Rho Guanine Nucleotide Exchange Factors
  • Receptors, G-Protein-Coupled
  • Apoptosis
  • Survival Analysis
  • Cell Growth Processes
  • Gene Knockdown Techniques
  • GTP Phosphohydrolases
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