文章：

YAP/TAZ信号网络在肿瘤进展与转移中的多功能调控作用

Multi-Functional Regulation by YAP/TAZ Signaling Networks in Tumor Progression and Metastasis

原文发布日期：24 September 2023

DOI: 10.3390/cancers15194701

类型: Article

开放获取: 是

英文摘要：

The Hippo pathway transcriptional co-activators, YES-associated protein (YAP) and Transcriptional Co-Activator with PDZ Binding Motif (TAZ), have both been linked to tumor progression and metastasis. These two proteins possess overlapping and distinct functions, and their activities lead to the expression of genes involved in multiple cellular processes, including cell proliferation, survival, and migration. The dysregulation of YAP/TAZ-dependent cellular processes can result in altered tumor growth and metastasis. In addition to their well-documented roles in the regulation of cancer cell growth, survival, migration, and invasion, the YAP/TAZ-dependent signaling pathways have been more recently implicated in cellular processes that promote metastasis and therapy resistance in several solid tumor types. This review highlights the role of YAP/TAZ signaling networks in the regulation of tumor cell plasticity mediated by hybrid and reversible epithelial–mesenchymal transition (EMT) states, and the promotion of cancer stem cell/progenitor phenotypes. Mechanistically, YAP and TAZ regulate these cellular processes by targeting transcriptional networks. In this review, we detail recently uncovered mechanisms whereby YAP and TAZ mediate tumor growth, metastasis, and therapy resistance, and discuss new therapeutic strategies to target YAP/TAZ function in various solid tumor types. Understanding the distinct and overlapping roles of YAP and TAZ in multiple cellular processes that promote tumor progression to metastasis is expected to enable the identification of effective therapies to treat solid tumors through the hyper-activation of YAP and TAZ.

摘要翻译： 

Hippo通路转录共激活因子YES相关蛋白（YAP）和具有PDZ结合基序的转录共激活因子（TAZ）均与肿瘤进展和转移密切相关。这两种蛋白具有重叠且独特的功能，其活性可调控多种细胞过程相关基因的表达，包括细胞增殖、存活和迁移。YAP/TAZ依赖性细胞过程的失调可能导致肿瘤生长和转移的改变。除了在调控癌细胞生长、存活、迁移和侵袭中已被充分证实的作用外，YAP/TAZ依赖性信号通路最近还被发现参与促进多种实体瘤转移和治疗抵抗的细胞过程。本综述重点阐述YAP/TAZ信号网络在调控由混合可逆上皮-间质转化（EMT）状态介导的肿瘤细胞可塑性，以及促进癌症干细胞/祖细胞表型中的作用。从机制上讲，YAP和TAZ通过靶向转录网络来调控这些细胞过程。本文详细阐述了近期发现的YAP和TAZ介导肿瘤生长、转移和治疗抵抗的机制，并讨论了针对不同实体瘤类型中YAP/TAZ功能的新型治疗策略。理解YAP和TAZ在促进肿瘤进展至转移的多个细胞过程中的独特及重叠作用，有望通过靶向YAP和TAZ的过度激活来确立治疗实体瘤的有效疗法。

原文链接：

Multi-Functional Regulation by YAP/TAZ Signaling Networks in Tumor Progression and Metastasis