YAP/TAZ Signaling as a Molecular Link between Fibrosis and Cancer.
YAP/TAZ Signaling as a Molecular Link between Fibrosis and Cancer.
复制标题
YAP/TAZ信号在纤维化和癌症之间的分子联系。
DOI：
10.3390/ijms19113674
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发表时间：
2018-11-20
影响因子：
5.6
通讯作者：
Nagase T
中科院分区：
文献类型：
--
作者：
Noguchi S;Saito A;Nagase T
组织纤维化是一种病理状态，与上皮修复受损和细胞外基质(ECM)过度沉积有关。纤维性病变增加了各种组织中的癌症风险，但纤维化与癌症之间的联系机制尚不清楚。是相关蛋白(YAP)和带有PDZ结合基序的转录共激活因子(TAZ)是河马途径的核心组成部分，它们在组织器官的发育、动态平衡和再生中具有多种生物学功能。YAP/TAZ是细胞微环境结构和力学特征的传感器。最近的研究表明，在动物模型和人类组织中，YAP/TAZ在纤维化和癌症中都存在异常激活。在成纤维细胞中，ECM刚性机制激活YAP/TAZ，促进促纤维化介质和ECM蛋白的产生。这会导致组织僵硬，从而建立成纤维细胞激活和组织纤维化的前馈循环。相反，在上皮细胞中，YAP/TAZ被纤维组织中细胞极性的破坏和ECM硬度的增加所激活，从而促进了上皮细胞的增殖和存活。YAP/TAZ还参与了上皮-间充质转化(EMT)，这有助于肿瘤的进展和癌症的干性。重要的是，与转化生长因子-β信号和Wnt信号的串扰对于YAP/TAZ的促纤维化和致癌作用是必不可少的。在本文中，我们综述了YAP/TAZ信号的病理生物学作用及其在纤维化和癌症之间的分子联系的最新进展。
Tissue fibrosis is a pathological condition that is associated with impaired epithelial repair and excessive deposition of extracellular matrix (ECM). Fibrotic lesions increase the risk of cancer in various tissues, but the mechanism linking fibrosis and cancer is unclear. Yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are core components of the Hippo pathway, which have multiple biological functions in the development, homeostasis, and regeneration of tissues and organs. YAP/TAZ act as sensors of the structural and mechanical features of the cell microenvironment. Recent studies have shown aberrant YAP/TAZ activation in both fibrosis and cancer in animal models and human tissues. In fibroblasts, ECM stiffness mechanoactivates YAP/TAZ, which promote the production of profibrotic mediators and ECM proteins. This results in tissue stiffness, thus establishing a feed-forward loop of fibroblast activation and tissue fibrosis. In contrast, in epithelial cells, YAP/TAZ are activated by the disruption of cell polarity and increased ECM stiffness in fibrotic tissues, which promotes the proliferation and survival of epithelial cells. YAP/TAZ are also involved in the epithelial–mesenchymal transition (EMT), which contributes to tumor progression and cancer stemness. Importantly, the crosstalk with transforming growth factor (TGF)-β signaling and Wnt signaling is essential for the profibrotic and tumorigenic roles of YAP/TAZ. In this article, we review the latest advances in the pathobiological roles of YAP/TAZ signaling and their function as a molecular link between fibrosis and cancer.
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影响因子：
5.2
作者：
Chakraborty S;Hong W
通讯作者：
Hong W
影响因子：
10.5
作者：
Cai J;Maitra A;Anders RA;Taketo MM;Pan D
通讯作者：
Pan D
影响因子：
50.3
作者：
Calon A;Espinet E;Palomo-Ponce S;Tauriello DV;Iglesias M;Céspedes MV;Sevillano M;Nadal C;Jung P;Zhang XH;Byrom D;Riera A;Rossell D;Mangues R;Massagué J;Sancho E;Batlle E
通讯作者：
Batlle E
影响因子：
21.3
作者：
通讯作者：
--
DOI：
10.1146/annurev-pathol-052016-100322
发表时间：
2017-01-24
期刊：
Annual review of pathology
影响因子：
--
作者：
Affo S;Yu LX;Schwabe RF
通讯作者：
Schwabe RF