文章：

YAP和TAZ：肿瘤微环境的信号中枢

YAP and TAZ: a signalling hub of the tumour microenvironment

原文发布日期：2019-07-03

DOI: 10.1038/s41568-019-0168-y

类型: Review Article

开放获取: 否

英文摘要：

YAP and TAZ are transcriptional activators pervasively induced in several human solid tumours and their functions in cancer cells are the focus of intense investigation. These studies established that YAP and TAZ are essential to trigger numerous cell-autonomous responses, such as sustained proliferation, cell plasticity, therapy resistance and metastasis. Yet tumours are complex entities, wherein cancer cells are just one of the components of a composite “tumour tissue”. The other component, the tumour stroma, is composed of an extracellular matrix with aberrant mechanical properties and other cell types, including cancer-associated fibroblasts and immune cells. The stroma entertains multiple and bidirectional interactions with tumour cells, establishing dependencies essential to unleash tumorigenesis. The molecular players of such interplay remain partially understood. Here, we review the emerging role of YAP and TAZ in choreographing tumour–stromal interactions. YAP and TAZ act within tumour cells to orchestrate responses in stromal cells. Vice versa, YAP and TAZ in stromal cells trigger effects that positively feed back on the growth of tumour cells. Recognizing YAP and TAZ as a hub of the network of signals exchanged within the tumour microenvironment provides a fresh perspective on the molecular principles of tumour self-organization, promising to unveil numerous new vulnerabilities.

摘要翻译： 

细胞衰老在肿瘤发生中起着关键作用。曾一度被部分研究者视为组织培养假象的衰老现象，如今已成为重要的研究领域。尽管存在共同的分子机制来维持这种表型特征性的生长停滞，但衰老的影响是多样化的，并且在某些情况下可能对肿瘤发生产生截然相反的作用。愈来愈明确的是，起源细胞及其所在组织决定了衰老对肿瘤发生的影响。本综述将通过聚焦以下方面来解析这一复杂性：衰老在初始肿瘤细胞与基质细胞中产生时如何影响肿瘤发生，以及这些作用在疾病进展的不同阶段如何变化。此外，我们重点探讨了衰老表型及其功能输出的多样性——超越生长停滞的衰老相关分泌表型（SASP）。值得庆幸的是，目前已开发出多种新型遗传学和药理学工具，使得我们能够进一步解析衰老表型。

原文链接：

YAP and TAZ: a signalling hub of the tumour microenvironment