title: Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma.
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.
authors.affiliation: Genetics Program, Michigan State University, 567 Wilson Road, Rm 2240E, East Lansing, Michigan 48824, USA.
authors.forename: Aritro
authors.initials: A
authors.lastname: Nath
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, 567 Wilson Road, Rm 2215, East Lansing, Michigan 48824, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Li
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, Minnesota 55905, USA.
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Roberts
authors.affiliation: Genetics Program, Michigan State University, 567 Wilson Road, Rm 2240E, East Lansing, Michigan 48824, USA.|Department of Microbiology and Molecular Genetics, Michigan State University, 567 Wilson Road, Rm 2215, East Lansing, Michigan 48824, USA.|Department of Chemical Engineering and Materials Science, Michigan State University, 428 South Shaw Lane, Rm 2527, East Lansing, Michigan 48824, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Chan
mesh_terms: D015415:Biomarkers; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018955:CD36 Antigens; D005230:Fatty Acids, Nonesterified; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins