G-protein-coupled receptors (GPCRs) and their ligands function in the progression of human malignancies. G12 and G13, encoded by GNA12 and GNA13, respectively, are referred to as the GEP oncogene and are implicated in tumor progression. However, the molecular mechanisms by which G12/13 activation promotes cancer progression are not fully elucidated. Here, we demonstrate elevated expression of G12/13 in human ovarian cancer tissues. G12/13 activation did not promote cellular migration in the ovarian cancer cell lines examined. Rather, G12/13 activation promoted cell growth. We used a synthetic biology approach using chimeric G proteins and GPCRs activated solely by artificial ligands to selectively trigger signaling pathways downstream of specific G proteins. We found that G12/13 promotes proliferation of ovarian cancer cells by activating the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway. Furthermore, we reveal that inhibition of YAP by short hairpin RNA or a specific inhibitor prevented the growth of ovarian cancer cells. Therefore, YAP may be a suitable therapeutic target in ovarian cancer.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cancer Research