title: GSK-3α Is a Novel Target of CREB and CREB-GSK-3α Signaling Participates in Cell Viability in Lung Cancer.
abstract: Overexpression or activation of cyclic AMP-response element-binding protein (CREB) has been known to be involved in several human malignancies, including lung cancer. Genes regulated by CREB have been reported to suppress apoptosis, induce cell proliferation, inflammation, and tumor metastasis. However, the critical target genes of CREB in lung cancer have not been well understood. Here, we identified GSK-3α as one of the CREB target genes which is critical for the viability of lung cancer cells. The CREB knockdown significantly reduced the expression of GSK-3α and the direct binding of CREB on the promoter of GSK3A was identified. Kaplan-Meier analysis with a public database showed a prognostic significance of aberrant GSK-3α expression in lung cancer. Inhibition of GSK-3α suppressed cell viability, colony formation, and tumor growth. For the first time, we demonstrated that GSK-3α is regulated by CREB in lung cancer and is required for the cell viability. These findings implicate CREB-GSK-3α axis as a novel therapeutic target for lung cancer treatment.
authors.affiliation: Section of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut, 06520, United States of America.
authors.forename: Sin-Aye
authors.initials: SA
authors.lastname: Park
authors.affiliation: Section of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut, 06520, United States of America.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Section of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut, 06520, United States of America.
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.affiliation: Section of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut, 06520, United States of America.|Developmental Therapeutics, Translational Research Program, Yale Comprehensive Cancer Center, New Haven, Connecticut, 06520, United States of America.
authors.forename: Ja Seok
authors.initials: JS
authors.lastname: Koo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011379:Prognosis; D015398:Signal Transduction
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha