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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 14-3-3t proteindependent 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.

Original languageEnglish
Pages (from-to)31923-31937
Number of pages15
JournalOncotarget
Volume8
Issue number19
DOIs
Publication statusPublished - 2017

Keywords

  • 14-3-3t
  • Apoptosis
  • Autophagy
  • Fhit
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology

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