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GEP oncogene promotes cell proliferation through YAP activation in ovarian cancer

Oncogene volume 35, pages 4471–4480 (2016)Cite this article

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Abstract

G-protein-coupled receptors (GPCRs) and their ligands function in the progression of human malignancies. Gα12 and Gα13, 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 Gα12/13 activation promotes cancer progression are not fully elucidated. Here, we demonstrate elevated expression of Gα12/13 in human ovarian cancer tissues. Gα12/13 activation did not promote cellular migration in the ovarian cancer cell lines examined. Rather, Gα12/13 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 Gα12/13 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.

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Acknowledgements

We are grateful to Ms Emiko Hori, Ms Yoko Miyanari and Research Support Center, Graduate School of Medical Science, Kyushu University for technical supports. This study was supported in part by a Grant-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (#24791709 and #26861332).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    H Yagi, K Asanoma, T Ohgami, A Ichinoe, K Sonoda & K Kato

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Correspondence to H Yagi.

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Yagi, H., Asanoma, K., Ohgami, T. et al. GEP oncogene promotes cell proliferation through YAP activation in ovarian cancer. Oncogene 35, 4471–4480 (2016). https://doi.org/10.1038/onc.2015.505

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