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YAP/TAZ: Drivers of Tumor Growth, Metastasis, and Resistance to Therapy.
BioEssays ( IF 3.2 ) Pub Date : 2020-03-04 , DOI: 10.1002/bies.201900162 Barry J Thompson 1
BioEssays ( IF 3.2 ) Pub Date : 2020-03-04 , DOI: 10.1002/bies.201900162 Barry J Thompson 1
Affiliation
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The transcriptional co-activators YAP (or YAP1) and TAZ (or WWTR1) are frequently activated during the growth and progression of many solid tumors, including lung, colorectal, breast, pancreatic, and liver carcinomas as well as melanoma and glioma. YAP/TAZ bind to TEAD-family co-activators to drive cancer cell survival, proliferation, invasive migration, and metastasis. YAP/TAZ activation may also confer resistance to chemotherapy, radiotherapy, or immunotherapy. YAP-TEAD cooperates with the RAS-induced AP-1 (FOS/JUN) transcription factor to drive tumor growth and cooperates with MRTF-SRF to promote activation of cancer-associated fibroblasts, matrix stiffening, and metastasis. The key upstream repressor of YAP/TAZ activation is the Hippo (MST1/2-LATS1/2) pathway and the key upstream activators are mechanically induced Integrin-SRC and E-cadherin-AJUBA/TRIP6/LIMD1, growth factor induced PI3K-AKT, and inflammation-induced G-protein coupled receptor (GPCR) signals, all of which antagonize the Hippo pathway. In this review, strategies to target YAP/TAZ activity in cancer are discussed along with the prospects for synergy with established pillars of cancer therapy.
中文翻译：
YAP/TAZ：肿瘤生长、转移和耐药性的驱动因素。
转录共激活因子 YAP（或 YAP1）和 TAZ（或 WWTR1）在许多实体瘤的生长和进展过程中经常被激活，包括肺癌、结直肠癌、乳腺癌、胰腺癌和肝癌以及黑色素瘤和神经胶质瘤。YAP/TAZ 与 TEAD 家族共激活剂结合以驱动癌细胞存活、增殖、侵袭性迁移和转移。YAP/TAZ 激活也可能赋予对化学疗法、放射疗法或免疫疗法的抵抗力。YAP-TEAD 与 RAS 诱导的 AP-1 (FOS/JUN) 转录因子协同驱动肿瘤生长，并与 MRTF-SRF 协同促进癌症相关成纤维细胞的激活、基质硬化和转移。YAP/TAZ 激活的关键上游抑制因子是 Hippo (MST1/2-LATS1/2) 通路，关键上游激活因子是机械诱导的 Integrin-SRC 和 E-cadherin-AJUBA/TRIP6/LIMD1，生长因子诱导的 PI3K-AKT和炎症诱导的 G 蛋白偶联受体 (GPCR) 信号，所有这些信号都拮抗 Hippo 通路。在这篇综述中，讨论了针对癌症中 YAP/TAZ 活性的策略，以及与已建立的癌症治疗支柱的协同作用的前景。
更新日期：2020-04-22
中文翻译：
YAP/TAZ：肿瘤生长、转移和耐药性的驱动因素。
转录共激活因子 YAP（或 YAP1）和 TAZ（或 WWTR1）在许多实体瘤的生长和进展过程中经常被激活，包括肺癌、结直肠癌、乳腺癌、胰腺癌和肝癌以及黑色素瘤和神经胶质瘤。YAP/TAZ 与 TEAD 家族共激活剂结合以驱动癌细胞存活、增殖、侵袭性迁移和转移。YAP/TAZ 激活也可能赋予对化学疗法、放射疗法或免疫疗法的抵抗力。YAP-TEAD 与 RAS 诱导的 AP-1 (FOS/JUN) 转录因子协同驱动肿瘤生长，并与 MRTF-SRF 协同促进癌症相关成纤维细胞的激活、基质硬化和转移。YAP/TAZ 激活的关键上游抑制因子是 Hippo (MST1/2-LATS1/2) 通路，关键上游激活因子是机械诱导的 Integrin-SRC 和 E-cadherin-AJUBA/TRIP6/LIMD1，生长因子诱导的 PI3K-AKT和炎症诱导的 G 蛋白偶联受体 (GPCR) 信号，所有这些信号都拮抗 Hippo 通路。在这篇综述中，讨论了针对癌症中 YAP/TAZ 活性的策略，以及与已建立的癌症治疗支柱的协同作用的前景。
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