Heterotrimeric G-Protein, G(alpha 16), Is a Critical Downstream Effector of Non-Canonical Wnt Signaling and a Potent Inhibitor of Transformed Cell Growth in Non Small Cell Lung Cancer
- Title
- Heterotrimeric G-Protein, G(alpha 16), Is a Critical Downstream Effector of Non-Canonical Wnt Signaling and a Potent Inhibitor of Transformed Cell Growth in Non Small Cell Lung Cancer
- Author
- 손장원
- Keywords
- ACTIVATED-RECEPTOR-GAMMA; EPITHELIAL-MESENCHYMAL TRANSITIONS; COUPLED RECEPTORS; TERATOCARCINOMA CELLS; RAT FRIZZLED-1; TCF PATHWAY; CYCLIC-GMP; KINASE; EXPRESSION; TRANSDUCTION
- Issue Date
- 2013-10
- Publisher
- PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
- Citation
- PLOS ONE,20132,8(10),p
- Abstract
- 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, PPAR gamma. 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 G(alpha 16) as a novel downstream effector of Wnt7a/Frizzled9 signaling. Interestingly, G(alpha 16) 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 G(alpha 16), we also establish G(alpha 16) 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 G(alpha 16) 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.
- URI
- http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076895http://hdl.handle.net/20.500.11754/42056
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0076895
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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