Although Hippo-YAP/TAZ pathway involvement has been extensively studied in the development of certain cancers, the involvement of this cascade in kidney cancer progression is not well-established and, therefore, will be the focus of this review. Renal cell carcinoma (RCC), the most prevalent kidney tumor subtype, has a poor prognosis and a high mortality rate. Core Hippo signaling inactivation (e.g., LATS kinases) leads to the nuclear translocation of YAP/TAZ where they bind to co-transcriptional factors such as TEAD promoting transcription of genes which initiates various fibrotic and neoplastic diseases. Loss of expression of LATS1/2 kinase and activation of YAP/TAZ correlates with poor survival in RCC patients. Renal-specific ablation of LATS1 in mice leads to the spontaneous development of several subtypes of RCC in a YAP/TAZ-dependent manner. Genetic and pharmacological inactivation of YAP/TAZ reverses the oncogenic potential in LATS1-deficient mice, highlighting the therapeutic benefit of network targeting in RCC. Here, we explore the unique upstream controls and downstream consequences of the Hippo-YAP/TAZ pathway deregulation in renal cancer. This review critically evaluates the current literature on the role of the Hippo pathway in RCC progression and highlights the recent scientific evidence designating YAP/TAZ as novel therapeutic targets against kidney cancer.
尽管Hippo-YAP/TAZ通路在多种癌症发展中的作用已被广泛研究，但该信号级联在肾癌进展中的参与机制尚未明确，因此将成为本综述的焦点。肾细胞癌作为最常见的肾脏肿瘤亚型，具有预后差、死亡率高的特点。Hippo核心信号失活（如LATS激酶）会导致YAP/TAZ核转位，进而与TEAD等共转录因子结合，启动促纤维化和肿瘤性疾病的基因转录。在肾细胞癌患者中，LATS1/2激酶表达缺失与YAP/TAZ激活与不良生存率显著相关。小鼠肾脏特异性敲除LATS1会以YAP/TAZ依赖的方式自发形成多种肾细胞癌亚型。通过遗传或药理学手段抑制YAP/TAZ可逆转LATS1缺陷小鼠的致癌潜能，这凸显了靶向该信号网络在肾细胞癌治疗中的潜在价值。本文系统探讨了Hippo-YAP/TAZ通路在肾癌中失调的特异性上游调控机制与下游效应，批判性评估了该通路在肾细胞癌进展中作用的现有文献，并重点阐述了将YAP/TAZ作为肾癌新型治疗靶点的最新科学依据。
肿瘤(癌症)患者之家