Benhammou Jihane N, Sinnett-Smith Jim, Pisegna Joseph R, Rozengurt Enrique J
Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California.
Division of Gastroenterology, Hepatology and Parenteral Nutrition, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California.
Gastro Hep Adv. 2022 Aug 3;2(2):232-241. doi: 10.1016/j.gastha.2022.07.017. eCollection 2023.
Nonalcoholic fatty liver disease has reached pandemic proportions with one of its most consequential complications being hepatocellular carcinoma (HCC). Nonalcoholic fatty liver disease-related HCC is becoming the leading indication for liver transplantation in the United States. Given the scarcity of available organs, early detection and prevention remain key in prevention and management of the disease. Over the years, the yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) pathway emerged as a key signal transduction pathway in the pathogenesis of HCC. In this review, we explore the interplay between the YAP/TAZ pathway as a point of convergence in HCC pathogenesis. We review the evidence of how lipid reprogramming and key lipid pathways, saturated and monounsaturated fatty acids (through the rate-limiting enzyme stearoyl Co-A desaturase), the mevalonic acid pathway (the role of statins), and mechanistic target of rapamycin all play critical roles in intricate and complex networks that tightly regulate the YAP/TAZ pro-oncogenic pathway.
非酒精性脂肪性肝病已呈大流行态势，其最严重的并发症之一是肝细胞癌（HCC）。非酒精性脂肪性肝病相关的肝细胞癌正成为美国肝移植的主要指征。鉴于可用器官稀缺，早期检测和预防仍然是该疾病预防和管理的关键。多年来，Yes相关蛋白（YAP）/具有PDZ结合基序的转录共激活因子（TAZ）信号通路已成为肝细胞癌发病机制中的关键信号转导通路。在这篇综述中，我们探讨YAP/TAZ信号通路作为肝细胞癌发病机制汇聚点的相互作用。我们回顾了脂质重编程和关键脂质信号通路、饱和脂肪酸和单不饱和脂肪酸（通过限速酶硬脂酰辅酶A去饱和酶）、甲羟戊酸途径（他汀类药物的作用）以及雷帕霉素靶蛋白如何在紧密调节YAP/TAZ促癌信号通路的复杂网络中发挥关键作用的证据。
