Driskill Jordan H, Dermawan Josephine K, Antonescu Cristina R, Pan Duojia
Department of Physiology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
Annu Rev Cancer Biol. 2024 Jun;8:331-350. doi: 10.1146/annurev-cancerbio-061223-094639.
Gene fusions are well-known drivers of cancer and are potent targets for molecular therapy. An emerging spectrum of human tumors harbors recurrent and pathognomonic gene fusions that involve the transcriptional coactivator (which encodes the protein YAP) or its paralog (which encodes the protein TAZ). YAP and TAZ are frequently activated in cancer and are the transcriptional effectors of the Hippo pathway, a highly conserved kinase cascade that regulates diverse functions such as organ size, development, and homeostasis. In this review, we discuss the tumors that have YAP, TAZ, or other Hippo-dysregulating fusion proteins; the mechanisms of these fusion proteins in driving their respective tumors; and the potential vulnerabilities of these chimeric oncoproteins across cancers of many origins. Furthermore, as new and gene fusions are discovered, we provide a framework to predict whether the resulting protein product is likely to be oncogenic.
基因融合是众所周知的癌症驱动因素，也是分子治疗的有效靶点。越来越多的人类肿瘤中存在复发性且具有病理诊断意义的基因融合，这些融合涉及转录共激活因子（编码YAP蛋白）或其旁系同源物（编码TAZ蛋白）。YAP和TAZ在癌症中经常被激活，并且是Hippo信号通路的转录效应器，Hippo信号通路是一种高度保守的激酶级联反应，可调节多种功能，如器官大小、发育和体内平衡。在这篇综述中，我们讨论了含有YAP、TAZ或其他Hippo信号失调融合蛋白的肿瘤；这些融合蛋白驱动各自肿瘤发生的机制；以及这些嵌合癌蛋白在多种起源癌症中的潜在弱点。此外，随着新的 和 基因融合的发现，我们提供了一个框架来预测产生的蛋白质产物是否可能具有致癌性。
