Implication of the Hedgehog pathway in hepatocellular carcinoma.
Implication of the Hedgehog pathway in hepatocellular carcinoma.
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DOI：
10.3748/wjg.v23.i24.4330
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发表时间：
2017-06-28
影响因子：
4.3
通讯作者：
Morgillo F
中科院分区：
文献类型：
--
作者：
Della Corte CM;Viscardi G;Papaccio F;Esposito G;Martini G;Ciardiello D;Martinelli E;Ciardiello F;Morgillo F
被诊断患有晚期肝细胞癌（HCC）的患者的预后很差，因为治疗选择很少。最近的研究重点是识别新的分子实体，这些实体可以靶向抑制参与 HCC 的致癌、增殖和进展的致癌信号。在参与 HCC 发展的所有途径中，Hedgehog (HH) 信号传导已被证明在肝癌发生和 HCC 进展中发挥着重要作用。 HH 通过诱导内胚层祖细胞分化为肝细胞，在胚胎发生中发挥生理作用。慢性受损肝脏中 HH 通路的重新激活是纤维变性的一种机制，与 HCC 发展的各个阶段有关。 HH 激活维持参与肝硬化和 HCC 发病机制的未成熟肝上皮细胞亚群，并且 HH 本身是酒精源性肝细胞恶性转化的介质。肝肿瘤组织中 HH 蛋白标记物的高水平表达与侵袭性组织学和生物学特征以及不良的临床结果相关。 HH 通路的体外和体内抑制模型证实，HH 对于维持肿瘤生长、转移和间充质表型至关重要。
The prognosis for patients who are diagnosed with advanced stage hepatocellular carcinoma (HCC) is poor because there are few treatment options. Recent research has focused on the identification of novel molecular entities that can be targeted to inhibit oncogenic signals that are involved in the carcinogenesis, proliferation and progression of HCC. Among all of the pathways that are involved in the development of HCC, Hedgehog (HH) signalling has demonstrated a substantial role in hepatocarcinogenesis and HCC progression. HH plays a physiological role in embryogenesis, through the induction of the differentiation of hepatocytes from endodermal progenitors. The re-activation of the HH pathway in chronic damaged liver is a mechanism of fibrotic degeneration and is implicated in various stages of HCC development. HH activation sustains the sub-population of immature liver epithelial cells that are involved in the pathogenesis of cirrhosis and HCC, and HH itself is a mediator of the alcohol-derived malignant transformation of liver cells. High levels of expression of HH protein markers in liver tumour tissues are correlated with aggressive histological and biological features and a poor clinical outcome. In vitro and in vivo inhibition models of the HH pathway confirm that HH is essential in maintaining tumour growth, metastasis and a mesenchymal phenotype.