Division of Medical Oncology B,Regina Elena National Cancer Institute,Rome,Italy.
Department of Hematology,Oncology and Molecular Medicine,Istituto Superiore di Sanità,Rome,Italy.
Expert Rev Mol Med. 2015 Jul 2;17:e14. doi: 10.1017/erm.2015.12.
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.
Hippo 信号通路正在成为一种肿瘤抑制途径,其功能受到细胞内和细胞外复杂网络的调节。信号级联的缺陷导致 Hippo 转导子 TAZ 和 YAP 的激活。令人信服的临床前证据表明,TAZ/YAP 在乳腺癌(BC)中经常异常参与,其过度激活最终导致多种促进肿瘤的功能,如上皮-间充质转化、癌症干细胞生成和治疗耐药性。对 TAZ/YAP 的生物学特性及其引发的分子产物有了更深入的了解,促使人们进行了第一批探索性的、以临床为重点的分析,旨在初步提示其表达的预后/预测意义。在这篇综述中,我们讨论了 TAZ/YAP 与 BC 相关的致癌活性,并提出了用于研究其作为生物标志物在临床环境中的作用的临床策略。最后,我们讨论了针对 TAZ/YAP 的治疗潜力以及我们认为应该追求的方式,以进一步研究其抑制的生物学和临床后果。