title: Fhit, a tumor suppressor protein, induces autophagy via 14-3-3τ in non-small cell lung cancer cells.
abstract: Inactivation of the fragile histidine triad (Fhit) gene has been reported in the majority of human cancers, particularly in lung cancer. The role of Fhit as a tumor suppressor gene has been well documented, and restoration of Fhit expression suppresses tumorigenicity in tumor cell lines and in mouse models by inducing apoptosis and inhibiting proliferation of tumor cells. Autophagy is a catabolic pathway, whereby cytoplasmic proteins and organelles are sequestered in vacuoles and delivered to lysosomes for degradation and recycling. Although autophagy is necessary for cell survival under stress conditions, recent studies have shown that autophagy can also promote cell death. Due to the fact that both autophagy induction and Fhit expression are commonly associated with nutrient starvation, we hypothesized that Fhit expression may be related to autophagy induction. In the present study, we assessed whether Fhit overexpression by gene transfer induces autophagy in Fhit-deficient non-small cell lung cancer (NSCLC) cells. The results of our study indicate that Fhit protein induces autophagy in NSCLC cells, and that this autophagy prevents apoptotic cell death in vivo and in vitro in a 14-3-3τ protein-dependent manner. To the best of our knowledge, this is the first report to describe Fhit-induced autophagy. Suppressing autophagy might be a promising therapeutic option to enhance the efficacy of Fhit gene therapy in NSCLC.
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.|School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Tae-Gul
authors.initials: TG
authors.lastname: Lee
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Eun-Hui
authors.initials: EH
authors.lastname: Jeong
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Seo Yun
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Hye-Ryoun
authors.initials: HR
authors.lastname: Kim
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Cheol-Hyeon
authors.initials: CH
authors.lastname: Kim
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism; D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D048948:14-3-3 Proteins; D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D000099170:Bis(5'-adenosyl)triphosphatase
keywords: 14-3-3τ; Fhit; apoptosis; autophagy; non-small cell lung cancer