Research Papers:

Fhit, a tumor suppressor protein, induces autophagy via 14-3-3τ in non-small cell lung cancer cells

Tae-Gul Lee, Eun-Hui Jeong, Seo Yun Kim, Hye-Ryoun Kim, Hyunggee Kim and Cheol-Hyeon Kim _

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Oncotarget. 2017; 8:31923-31937. https://doi.org/10.18632/oncotarget.16652

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Tae-Gul Lee1,2, Eun-Hui Jeong1, Seo Yun Kim1, Hye-Ryoun Kim1, Hyunggee Kim2, Cheol-Hyeon Kim1

1Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea

2School of Life Sciences and Biotechnology, Korea University, Seoul, Korea

Correspondence to:

Cheol-Hyeon Kim, email: [email protected]

Keywords: Fhit, autophagy, 14-3-3τ, non-small cell lung cancer, apoptosis

Received: September 23, 2016     Accepted: March 16, 2017     Published: March 29, 2017


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.

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