Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma

Jian Min Wu, Yan Xu, N. Skill, Hongmiao Sheng, Zhenwen Zhao, Menggang Yu, Romil Saxena, Mary Maluccio

Research output: Contribution to journalArticle

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Abstract

Background: Autotaxin (ATX) is an extracellular lysophospholipase D that generates lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Both ATX and LPA have been shown to be involved in many cancers. However, the functional role of ATX and the regulation of ATX expression in human hepatocellular carcinoma (HCC) remain elusive.Results: In this study, ATX expression was evaluated in tissues from 38 human HCC and 10 normal control subjects. ATX was detected mainly in tumor cells within tissue sections and its over-expression in HCC was specifically correlated with inflammation and liver cirrhosis. In addition, ATX expression was examined in normal human hepatocytes and liver cancer cell lines. Hepatoma Hep3B and Huh7 cells displayed stronger ATX expression than hepatoblastoma HepG2 cells and normal hepatocytes did. Proinflammtory cytokine tumor necrosis factor alpha (TNF-α) promoted ATX expression and secretion selectively in Hep3B and Huh7 cells, which led to a corresponding increase in lysophospholipase-D activity. Moreover, we explored the mechanism governing the expression of ATX in hepatoma cells and established a critical role of nuclear factor-kappa B (NF-κB) in basal and TNF-α induced ATX expression. Further study showed that secreted enzymatically active ATX stimulated Hep3B cell invasion.Conclusions: This report highlights for the first time the clinical and biological evidence for the involvement of ATX in human HCC. Our observation that links the TNF-α/NF-κB axis and the ATX-LPA signaling pathway suggests that ATX is likely playing an important role in inflammation related liver tumorigenesis.

Original languageEnglish
Article number71
JournalMolecular Cancer
Volume9
DOIs
StatePublished - Mar 31 2010

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NF-kappa B
Hepatocellular Carcinoma
Tumor Necrosis Factor-alpha
Hepatocytes
Inflammation
Hepatoblastoma
Lysophosphatidylcholines
Hep G2 Cells
Liver Neoplasms
Liver Cirrhosis
Neoplasms
Carcinogenesis
Cytokines
Cell Line
Liver
lysophosphatidic acid

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

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Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma. / Wu, Jian Min; Xu, Yan; Skill, N.; Sheng, Hongmiao; Zhao, Zhenwen; Yu, Menggang; Saxena, Romil; Maluccio, Mary.

In: Molecular Cancer, Vol. 9, 71, 31.03.2010.

Research output: Contribution to journalArticle

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