RRC ID 63415
Author Yagi H, Asanoma K, Ohgami T, Ichinoe A, Sonoda K, Kato K.
Title GEP oncogene promotes cell proliferation through YAP activation in ovarian cancer.
Journal Oncogene
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.
Volume 35(34)
Pages 4471-80
Published 2016-8-25
DOI 10.1038/onc.2015.505
PII onc2015505
PMID 26804165
MeSH Active Transport, Cell Nucleus Adaptor Proteins, Signal Transducing / analysis Adaptor Proteins, Signal Transducing / antagonists & inhibitors Adaptor Proteins, Signal Transducing / physiology* Animals Cell Line, Tumor Cell Proliferation* Female GTP-Binding Protein alpha Subunits, G12-G13 / genetics* GTP-Binding Protein alpha Subunits, G12-G13 / physiology Hippo Signaling Pathway Humans Mice Mice, Inbred BALB C Oncogenes* Ovarian Neoplasms / chemistry Ovarian Neoplasms / genetics* Ovarian Neoplasms / pathology Phosphoproteins / analysis Phosphoproteins / antagonists & inhibitors Phosphoproteins / physiology* Phosphorylation Protein Serine-Threonine Kinases / metabolism Protein Serine-Threonine Kinases / physiology Transcription Factors YAP-Signaling Proteins
IF 7.971
Human and Animal Cells OVK18(RCB1903)