Transforming growth factor-β-induced plasticity causes a migratory sternness phenotype in hepatocellular carcinoma
Transforming growth factor-β-induced plasticity causes a migratory sternness phenotype in hepatocellular carcinoma
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DOI：
10.1016/j.canlet.2017.01.037
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发表时间：
2017-04-28
期刊：
影响因子：
9.7
通讯作者：
Fabregat, Isabel
中科院分区：
文献类型：
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作者：
Malfettone, Andrea;Soukupova, Jitka;Fabregat, Isabel
作为其潜在促肿瘤作用的一部分，转化生长因子-(TGF)-β 可诱导肝细胞癌 (HCC) 细胞上皮间质转化 (EMT)。 EMT是否会引起肿瘤细胞可塑性的变化尚未得到充分探索。在这里，我们分析了 TGF-β 对 HCC 细胞 EMT 和干相关特性的影响以及这些过程之间的潜在相关性。该研究的转化目的是提出 TGF-β/EMT/stem 基因特征，有助于将 HCC 患者视为抗 TGF-β 治疗的良好候选者。结果表明，当 TGF-β 诱导 HCC 细胞发生 EMT 时，可观察到干基因表达的转变，并且其干性潜力和迁移/侵袭能力增强。然而，TGF-β可能在一些上皮性肝癌细胞中诱导部分EMT，增加间质基因和CD44的表达，但维持上皮基因的表达。上皮细胞比间充质细胞表现出更高的干性潜力，但对 TGF-β 的反应增加了它们的迁移和侵袭能力。在 HCC 患者样本中，TGFBI 表达最常与部分 EMT、间充质基因和 CD44 表达增加以及上皮相关基因的维持或过度表达相关。 (C) 2017 Elsevier B.V. 保留所有权利。
As part of its potential pro-tumorigenic actions, Transforming Growth Factor-(TGF)-beta induces epithelial mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells. Whether EMT induces changes in tumor cell plasticity has not been fully explored yet. Here, we analyze the effects of TGF-beta on the EMT and stem-related properties of HCC cells and the potential correlation among those processes. The translational aim of the study was to propose a TGF-beta/EMT/stem gene signature that would help in recognizing HCC patients as good candidates for anti-TGF-beta therapy. Results indicate that when TGF-beta induces EMT in HCC cells, a switch in the expression of stem genes is observed and their sternness potential and migratory/invasive capacity are enhanced. However, TGF-beta may induce a partial EMT in some epithelial HCC cells, increasing the expression of mesenchymal genes and CD44, but maintaining epithelial gene expression. Epithelial cells show higher sternness potential than the mesenchymal ones, but respond to TGF-beta increasing their migratory and invasive capacity. In HCC patient samples, TGFBI expression most frequently correlates with a partial EMT, increase in mesenchymal genes and CD44 expression, as well as maintenance or over-expression of epithelial-related genes. (C) 2017 Elsevier B.V. All rights reserved.