Glutaminase 2 stabilizes Dicer to repress Snail and metastasis in hepatocellular carcinoma cells

Tsang Chih Kuo, Chi Kuan Chen, Kuo Tai Hua, Pei Yu, Wei-Jiunn Lee, Min Wei Chen, Yung Ming Jeng, Ming-Hsien Chien, Kuang-tai Kuo, Michael Hsiao, Min Liang Kuo

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Glutaminolysis that catabolizes glutamine to glutamate plays a critical role in cancer progression. Glutaminase 2 (GLS2) has been reported as a tumor suppressor. Recent studies implied that GLS2 may display its multifunction besides classical metabolic feature by different localizations and potential protein binding domains. Here, we showed that GLS2 expression correlates inversely with stage, vascular invasion, tumor size and poor prognosis in human hepatocellular carcinoma (HCC) tissues. We found that GLS2 significantly represses cell migration, invasion and metastasis of HCC through downregulation of Snail in vitro and in vivo. Moreover, our results demonstrated that GLS2 interacts with Dicer and stabilizes Dicer protein to facilitate miR-34a maturation and subsequently represses Snail expression in a glutaminase activity independent manner. Our findings indicate that non-glutaminolysis function of GLS2 inhibits migration and invasion of HCC cells by repressing the epithelial–mesenchymal transition via the Dicer-miR-34a-Snail axis.

Original languageEnglish
Pages (from-to)282-294
Number of pages13
JournalCancer Letters
Volume383
Issue number2
DOIs
Publication statusPublished - Dec 28 2016

Fingerprint

Glutaminase
Hepatocellular Carcinoma
Neoplasm Metastasis
Snails
Neoplasms
Glutamine
Protein Binding
Cell Movement
Blood Vessels
Glutamic Acid
Down-Regulation

Keywords

  • Dicer
  • Epithelial–mesenchymal transition
  • Glutaminase 2
  • Hepatocellular carcinoma cells
  • Snail

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Glutaminase 2 stabilizes Dicer to repress Snail and metastasis in hepatocellular carcinoma cells. / Kuo, Tsang Chih; Chen, Chi Kuan; Hua, Kuo Tai; Yu, Pei; Lee, Wei-Jiunn; Chen, Min Wei; Jeng, Yung Ming; Chien, Ming-Hsien; Kuo, Kuang-tai; Hsiao, Michael; Kuo, Min Liang.

In: Cancer Letters, Vol. 383, No. 2, 28.12.2016, p. 282-294.

Research output: Contribution to journalArticle

Kuo, Tsang Chih ; Chen, Chi Kuan ; Hua, Kuo Tai ; Yu, Pei ; Lee, Wei-Jiunn ; Chen, Min Wei ; Jeng, Yung Ming ; Chien, Ming-Hsien ; Kuo, Kuang-tai ; Hsiao, Michael ; Kuo, Min Liang. / Glutaminase 2 stabilizes Dicer to repress Snail and metastasis in hepatocellular carcinoma cells. In: Cancer Letters. 2016 ; Vol. 383, No. 2. pp. 282-294.
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