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: Contribution to journalArticle

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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.

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

Profile

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

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