Molecular Oncology Unit, CIEMAT (ed 70A), Av. Complutense 40, 28040 Madrid, Spain; Molecular Oncology, University Hospital 12 de Octubre, Research Institute 12 de Octubre i+12, Av. Córdoba s/n, 28041 Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain.
Molecular Oncology Unit, CIEMAT (ed 70A), Av. Complutense 40, 28040 Madrid, Spain; Molecular Oncology, University Hospital 12 de Octubre, Research Institute 12 de Octubre i+12, Av. Córdoba s/n, 28041 Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain.
Oral Oncol. 2018 Nov;86:25-32. doi: 10.1016/j.oraloncology.2018.08.020. Epub 2018 Sep 11.
The Hippo-YAP (Yes-associated protein) pathway is a key regulator of tissue growth, organ size and stem cell function. More recently, a fundamental role for this pathway has emerged in stem cell function and tumorigenesis. Activation of the transcriptional co-activator YAP promotes cell-contact independent proliferation, epithelial to mesenchymal transition (EMT), cancer stem cell features and drug resistance. In this review, we describe the main components of the pathway, the microenvironment and the cell-intrinsic cues governing its activation, the downstream players of the pathway and the biological implications of their activation in the context of cancer. We will focus on the existing knowledge of this pathway in head and neck squamous carcinoma (HNSCC), its clinical value in this type of cancer as a marker of poor prognosis and resistance to therapy, as well as the most encouraging therapeutic strategies targeting the pathway.
Hippo-YAP（Yes-associated protein）通路是组织生长、器官大小和干细胞功能的关键调节因子。最近，该通路在干细胞功能和肿瘤发生中具有重要作用。转录共激活因子 YAP 的激活促进细胞接触独立增殖、上皮-间充质转化（EMT）、癌症干细胞特征和耐药性。在这篇综述中，我们描述了该通路的主要组成部分、微环境和细胞内信号通路激活的调控因素、该通路的下游靶点及其在癌症背景下激活的生物学意义。我们将重点介绍该通路在头颈部鳞状细胞癌（HNSCC）中的现有知识，及其作为预后不良和治疗耐药标志物的临床价值，以及针对该通路最有前途的治疗策略。
