Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma

Aritro Nath, Irene Li, Lewis R. Roberts, Christina Chan

    Research output: Research - peer-reviewArticle

    • 19 Citations

    Abstract

    Hepatocellular carcinoma (HCC) is the second-leading cause of cancer-related death worldwide, and the factors influencing HCC progression are poorly understood. Here we reveal that HCC progression via induction of epithelial-mesenchymal transition (EMT) is closely associated with the expression of CD36/fatty acid translocase and elevated free fatty acid (FFA) levels. Although obesity is manifested as elevated FFA levels, the degree of EMT was not associated with the body mass index of the patients, highlighting the specific roles of CD36 and FFA uptake. Treatment of human liver cancer cell lines with FFAs exacerbated the EMT phenotype, whereas chemical inhibition of CD36 mitigated these effects. Furthermore, the Wnt and TGF-β signaling pathways were activated upon FFA treatment, potentially acting as upstream activators of the EMT program. These results provide the first direct evidence associating CD36 and elevated FFAs with HCC progression.

    LanguageEnglish (US)
    Article number14752
    JournalScientific Reports
    Volume5
    DOIs
    StatePublished - Oct 1 2015

    Profile

    Epithelial-Mesenchymal Transition
    Nonesterified Fatty Acids
    Hepatocellular Carcinoma
    Therapeutics
    Liver Neoplasms
    Transforming Growth Factor beta
    Body Mass Index
    Fatty Acids
    Obesity
    Phenotype
    Cell Line
    Neoplasms

    ASJC Scopus subject areas

    • General

    Cite this

    Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma. / Nath, Aritro; Li, Irene; Roberts, Lewis R.; Chan, Christina.

    In: Scientific Reports, Vol. 5, 14752, 01.10.2015.

    Research output: Research - peer-reviewArticle

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    abstract = "Hepatocellular carcinoma (HCC) is the second-leading cause of cancer-related death worldwide, and the factors influencing HCC progression are poorly understood. Here we reveal that HCC progression via induction of epithelial-mesenchymal transition (EMT) is closely associated with the expression of CD36/fatty acid translocase and elevated free fatty acid (FFA) levels. Although obesity is manifested as elevated FFA levels, the degree of EMT was not associated with the body mass index of the patients, highlighting the specific roles of CD36 and FFA uptake. Treatment of human liver cancer cell lines with FFAs exacerbated the EMT phenotype, whereas chemical inhibition of CD36 mitigated these effects. Furthermore, the Wnt and TGF-β signaling pathways were activated upon FFA treatment, potentially acting as upstream activators of the EMT program. These results provide the first direct evidence associating CD36 and elevated FFAs with HCC progression.",
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