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

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 hepato...

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Autores principales: Wu, Jian-Min, Xu, Yan, Skill, Nicholas J, Sheng, Hongmiao, Zhao, Zhenwen, Yu, Menggang, Saxena, Romil, Maluccio, Mary A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867819/
https://www.ncbi.nlm.nih.gov/pubmed/20356387
http://dx.doi.org/10.1186/1476-4598-9-71
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author Wu, Jian-Min
Xu, Yan
Skill, Nicholas J
Sheng, Hongmiao
Zhao, Zhenwen
Yu, Menggang
Saxena, Romil
Maluccio, Mary A
author_facet Wu, Jian-Min
Xu, Yan
Skill, Nicholas J
Sheng, Hongmiao
Zhao, Zhenwen
Yu, Menggang
Saxena, Romil
Maluccio, Mary A
author_sort Wu, Jian-Min
collection PubMed
description 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.
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spelling pubmed-28678192010-05-12 Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma Wu, Jian-Min Xu, Yan Skill, Nicholas J Sheng, Hongmiao Zhao, Zhenwen Yu, Menggang Saxena, Romil Maluccio, Mary A Mol Cancer Research 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. BioMed Central 2010-03-31 /pmc/articles/PMC2867819/ /pubmed/20356387 http://dx.doi.org/10.1186/1476-4598-9-71 Text en Copyright ©2010 Wu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Wu, Jian-Min
Xu, Yan
Skill, Nicholas J
Sheng, Hongmiao
Zhao, Zhenwen
Yu, Menggang
Saxena, Romil
Maluccio, Mary A
Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma
title Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma
title_full Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma
title_fullStr Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma
title_full_unstemmed Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma
title_short Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma
title_sort autotaxin expression and its connection with the tnf-alpha-nf-κb axis in human hepatocellular carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867819/
https://www.ncbi.nlm.nih.gov/pubmed/20356387
http://dx.doi.org/10.1186/1476-4598-9-71
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