Nath Aritro, Li Irene, Roberts Lewis R, Chan Christina
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.
Sci Rep. 2015 Oct 1;5:14752. doi: 10.1038/srep14752.
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.
肝细胞癌（HCC）是全球癌症相关死亡的第二大原因，而影响HCC进展的因素目前仍知之甚少。在此，我们揭示了通过诱导上皮-间质转化（EMT）导致的HCC进展与CD36/脂肪酸转运蛋白的表达及游离脂肪酸（FFA）水平升高密切相关。虽然肥胖表现为FFA水平升高，但EMT程度与患者的体重指数无关，这突出了CD36和FFA摄取的特定作用。用FFA处理人肝癌细胞系会加剧EMT表型，而对CD36的化学抑制则可减轻这些影响。此外，FFA处理后Wnt和TGF-β信号通路被激活，可能作为EMT程序的上游激活因子。这些结果提供了首个将CD36和升高的FFA与HCC进展相关联的直接证据。
