The Hippo pathway effectors yes-associated protein (YAP) and WW domain containing transcription regulator 1 (TAZ/WWTR1) support tumor initiation and progression in various cancer entities including hepatocellular carcinoma (HCC). However, to which extent YAP and TAZ contribute to liver tumorigenesis via common and exclusive molecular mechanisms is poorly understood. RNAinterference (RNAi) experiments illustrate that YAP and TAZ individually support HCC cell viability and migration, while for invasion additive effects were observed. Comprehensive expression profiling revealed partly overlapping YAP/TAZ target genes as well as exclusively regulated genes. Integrin-αV (ITGAV) is a novel TAZ-specific target gene, whose overexpression in human HCC patients correlates with poor clinical outcome, TAZ expression in HCCs, and the abundance of YAP/TAZ target genes. Functionally, ITGAV contributes to actin stress fiber assembly, tumor cell migration and invasion. Perturbation of ITGAV diminishes actin fiber formation and nuclear YAP/TAZ protein levels. We describe a novel Hippo downstream mechanism in HCC cells, which is regulated by TAZ and ITGAV and that feedbacks on YAP/TAZ activity. This mechanism may represent a therapeutic target structure since it contributes to signal amplification of oncogenic YAP/TAZ in hepatocarcinogenesis.

中文翻译：

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TAZ目标基因ITGAV调节肝癌细胞的侵袭并积极反馈YAP和TAZ。

Hippo途径效应子是相关蛋白（YAP）和包含转录调节因子1的WW域（TAZ / WWTR1）支持包括肝细胞癌（HCC）在内的各种癌症实体的肿瘤起始和进展。然而，人们对YAP和TAZ通过共同的和排他的分子机制在多大程度上促进肝肿瘤发生的了解很少。RNAi干扰（RNAi）实验表明，YAP和TAZ分别支持HCC细胞的活力和迁移，而对于侵袭性则观察到了加性效应。全面的表达谱分析显示部分重叠的YAP / TAZ靶基因以及专门受调控的基因。整合素αV（ITGAV）是一种新型的TAZ特异性靶基因，其在人类HCC患者中的过度表达与不良的临床预后，肝癌中TAZ的表达，和YAP / TAZ靶基因的丰富。从功能上讲，ITGAV有助于肌动蛋白应力纤维的组装，肿瘤细胞的迁移和侵袭。ITGAV的摄动可减少肌动蛋白纤维形成和核YAP / TAZ蛋白水平。我们描述了一种新型的河马下游机制在HCC细胞中，由TAZ和ITGAV调节，并反馈YAP / TAZ活性。该机制可代表治疗靶结构，因为它有助于肝癌发生中致癌性YAP / TAZ的信号放大。