Autocrine human growth hormone promotes invasive and cancer stem cell-like behavior of hepatocellular carcinoma cells by STAT3 dependent inhibition of CLAUDIN-1 expression

Yi Jun Chen, Ming Liang You, Qing Yun Chong, Vijay Pandey, Qiu Shi Zhuang, Dong Xu Liu, Lan Ma, Tao Zhu, Peter E. Lobie

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Despite progress in diagnosis and treatment of hepatocellular carcinoma (HCC), the clinical outcome is still unsatisfactory. Increased expression of human growth hormone (hGH) in HCC has been reported and is associated with poor survival outcome in HCC patients. Herein, we investigated the mechanism of the oncogenic effects of hGH in HCC cell lines. In vitro functional assays demonstrated that forced expression of hGH in these HCC cell lines promoted cell proliferation, cell survival, anchorage-independent growth, cell migration, and invasion, as previously reported. In addition, forced expression of hGH promoted cancer stem cell (CSC)-like properties of HCC cells. The increased invasive and CSC-like properties of HCC cells with forced expression of hGH were mediated by inhibition of the expression of the tight junction component CLAUDIN-1. Consistently, depletion of CLAUDIN-1 expression increased the invasive and CSClike properties of HCC cell lines. Moreover, forced expression of CLAUDIN-1 abrogated the acquired invasive and CSC-like properties of HCC cell lines with forced expression of hGH. We further demonstrated that forced expression of hGH inhibited CLAUDIN-1 expression in HCC cell lines via signal transducer and activator of transcription 3 (STAT3) mediated inhibition of CLAUDIN-1 transcription. Hence, we have elucidated a novel hGH-STAT3-CLAUDIN-1 axis responsible for invasive and CSC-like properties in HCC. Inhibition of hGH should be considered as a therapeutic option to hinder progression and relapse of HCC.

Original languageEnglish (US)
Article number1274
JournalInternational journal of molecular sciences
Volume18
Issue number6
DOIs
StatePublished - Jun 15 2017

Keywords

  • CLAUDIN-1
  • Cancer stem cells
  • Hepatocellular carcinoma
  • Human growth hormone
  • STAT3

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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