Focal Adhesion Kinase: Insight into Molecular Roles and Functions in Hepatocellular Carcinoma.
Focal Adhesion Kinase: Insight into Molecular Roles and Functions in Hepatocellular Carcinoma.
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DOI：
10.3390/ijms18010099
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发表时间：
2017-01-05
影响因子：
5.6
通讯作者：
Alisi A
中科院分区：
文献类型：
--
作者：
Panera N;Crudele A;Romito I;Gnani D;Alisi A
肝细胞癌（HCC）是全球癌症相关死亡的第三大原因。由于目前治疗后术后复发率高，需要寻找新的更有效的药物。近年来，在高通量测序技术的帮助下，已经发现了参与HCC发病机制的新的靶向基因/途径。TP53和β-连环蛋白基因突变是HCC中最常见的畸变。然而，能够逆转这些突变影响的方法可能是不可预测的。事实上，如果蛋白质的再激活，如肿瘤中的p53，作为抗癌治疗有很大的希望，有研究认为，这些类型的分子的慢性激活可能是有害的。因此，最近对潜在靶点的研究主要集中在可操作的突变上，例如那些发生在局灶黏附激酶（FAK）基因编码中的突变。这种酪氨酸激酶，定位于细胞局灶接触，在包括HCC在内的多种人类肿瘤中过度表达。此外，一些证据表明，FAK的缺失或抑制会损害体外和体内HCC的生长和转移。在这里，我们概述了FAK在肿瘤生物学背景下的表达和活性，讨论了其与HCC发生和进展相关的当前证据。
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Due to the high incidence of post-operative recurrence after current treatments, the identification of new and more effective drugs is required. In previous years, new targetable genes/pathways involved in HCC pathogenesis have been discovered through the help of high-throughput sequencing technologies. Mutations in TP53 and β-catenin genes are the most frequent aberrations in HCC. However, approaches able to reverse the effect of these mutations might be unpredictable. In fact, if the reactivation of proteins, such as p53 in tumours, holds great promise as anticancer therapy, there are studies arguing that chronic activation of these types of molecules may be deleterious. Thus, recently the efforts on potential targets have focused on actionable mutations, such as those occurring in the gene encoding for focal adhesion kinase (FAK). This tyrosine kinase, localized to cellular focal contacts, is over-expressed in a variety of human tumours, including HCC. Moreover, several lines of evidence demonstrated that FAK depletion or inhibition impair in vitro and in vivo HCC growth and metastasis. Here, we provide an overview of FAK expression and activity in the context of tumour biology, discussing the current evidence of its connection with HCC development and progression.