Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma.
Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal transition in hepatocellular carcinoma.
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DOI：
10.1038/srep14752
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发表时间：
2015-10-01
影响因子：
4.6
通讯作者：
Chan C
中科院分区：
文献类型：
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作者：
Nath A;Li I;Roberts LR;Chan C
肝细胞癌（HCC）是全球癌症相关死亡的第二大原因，而影响HCC进展的因素尚不明确。在此我们揭示，通过诱导上皮 - 间质转化（EMT）的HCC进展与CD36/脂肪酸转运蛋白的表达以及游离脂肪酸（FFA）水平升高密切相关。尽管肥胖表现为FFA水平升高，但EMT的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处理人肝癌细胞系加剧了EMT表型，而对CD36的化学抑制减轻了这些影响。此外，Wnt和TGF - β信号通路在FFA处理后被激活，可能作为EMT程序的上游激活因子。这些结果提供了将CD36和升高的FFA与HCC进展相关联的首个直接证据。
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.