Heterotrimeric G-Protein, Gα16, Is a Critical Downstream Effector of Non-Canonical Wnt Signaling and a Potent Inhibitor of Transformed Cell Growth in Non Small Cell Lung Cancer

• Published in: PloS one Vol. 8; no. 10; p. e76895
• Main Authors: Avasarala, Sreedevi, Bikkavilli, Rama Kamesh, Van Scoyk, Michelle, Zhang, Wei, Lapite, Ajibike, Hostetter, Logan, Byers, Joshua T., Heasley, Lynn E., Sohn, Jang Won, Winn, Robert A.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.10.2013; Public Library of Science (PLoS)
• Subjects: Biological activity; Cancer; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell growth; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell surface; Critical care; Enzyme Activation; Frizzled Receptors - genetics; Frizzled Receptors - metabolism; G protein-coupled receptors; Gene expression; Growth Inhibitors - genetics; Growth Inhibitors - metabolism; GTP-Binding Protein alpha Subunits, Gq-G11 - genetics; GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism; Guanosine triphosphatases; Guanosinetriphosphatase; Humans; Immunoblotting; Kinases; Lung cancer; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medicine; Mitogen-Activated Protein Kinase 7 - metabolism; mRNA; Mutation; PPAR gamma - metabolism; Proteins; Receptor Tyrosine Kinase-like Orphan Receptors - metabolism; Receptors; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; RNA Interference; Signal transduction; Signaling; Sleep; Tumor cell lines; Tumor suppressor genes; Wnt protein; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt Signaling Pathway; United States > US; Illinois; Chicago Illinois
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0076895

G-protein-coupled receptors (GPCR) are the largest family of cell surface molecules that play important role/s in a number of biological and pathological processes including cancers. Earlier studies have highlighted the importance of Wnt7a signaling via its cognate receptor Frizzled9, a GPCR, in inhibition of cell proliferation, anchorage-independent growth, and reversal of transformed phenotype in non small cell lung cancer primarily through activation of the tumor suppressor, PPARγ. However, the G-protein effectors that couple to this important tumor suppressor pathway have not been identified, and are of potential therapeutic interest. In this study, by using two independent Wnt7a/Frizzled9-specific read-outs, we identify Gα16 as a novel downstream effector of Wnt7a/Frizzled9 signaling. Interestingly, Gα16 expression is severely down-regulated, both at the messenger RNA levels and protein levels, in many non small cell lung cancer cell lines. Additionally, through gene-specific knock-downs and expression of GTPase-deficient forms (Q212L) of Gα16, we also establish Gα16 as a novel regulator of non small cell lung cancer cell proliferation and anchorage-independent cell growth. Taken together, our data not only establish the importance of Gα16 as a critical downstream effector of the non-canonical Wnt signaling pathway but also as a potential therapeutic target for the treatment of non small cell lung cancer.