The Hippo signalling is emerging as a tumour suppressor pathway whose function is regulated by an intricate network of intracellular and extracellular cues. Defects in the signal cascade lead to the activation of the Hippo transducers TAZ and YAP. Compelling preclinical evidence showed that TAZ/YAP are often aberrantly engaged in breast cancer (BC), where their hyperactivation culminates into a variety of tumour-promoting functions such as epithelial-to-mesenchymal transition, cancer stem cell generation and therapeutic resistance. Having acquired a more thorough understanding in the biology of TAZ/YAP, and the molecular outputs they elicit, has prompted a first wave of exploratory, clinically-focused analyses aimed at providing initial hints on the prognostic/predictive significance of their expression. In this review, we discuss oncogenic activities linked with TAZ/YAP in BC, and we propose clinical strategies for investigating their role as biomarkers in the clinical setting. Finally, we address the therapeutic potential of TAZ/YAP targeting and the modalities that, in our opinion, should be pursued in order to further study the biological and clinical consequences of their inhibition.

中文翻译：

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Hippo 换能器 TAZ 和 YAP 在乳腺癌中的作用：致癌活性和临床意义

Hippo 信号通路正在成为一种肿瘤抑制通路，其功能受细胞内和细胞外信号的复杂网络调节。信号级联中的缺陷导致 Hippo 传感器 TAZ 和 YAP 的激活。令人信服的临床前证据表明，TAZ/YAP 经常异常参与乳腺癌 (BC)，其中它们的过度激活最终导致各种肿瘤促进功能，例如上皮-间质转化、癌症干细胞生成和治疗抗性。在对 TAZ/YAP 的生物学及其引发的分子输出有了更透彻的了解后，引发了第一波探索性的、以临床为重点的分析，旨在为其表达的预后/预测意义提供初步提示。在本次审查中，我们讨论了与 BC 中的 TAZ/YAP 相关的致癌活性，并提出了临床策略来研究它们作为生物标志物在临床环境中的作用。最后，我们讨论了 TAZ/YAP 靶向的治疗潜力以及我们认为应该采用的方式，以进一步研究其抑制的生物学和临床后果。