摘要
YAP1和转录共激活因子与PDZ结合基序与许多转录因子一起调控基因转录。YAP1和TAZ由肿瘤抑制性的Hippo病理通路负面地调控,在人类肿瘤中,Hippo通路经常失去控制并且YAP1和TAZ能躲避Hippo通路的抑制,YAP1和TAZ的上调诱导了上皮细胞间质转化与肿瘤细胞耐药性增加。TAZ与肿瘤干细胞有关,结果是与高度表达的YAP1和TAZ肿瘤与临床预后有关。YAP1和TAZ的抑制剂被认为在肿瘤治疗中是有益的。另一方面,因为YAP1和TAZ在各种组织干细胞和组织修复的调节中起着非常重要的角色,YAP1和TAZ的激活物在再生医学中很有用。本文讨论了YAP1和TAZ的抑制剂和激活剂在人类疾病中潜在的应用和综述了检索这些制剂的药物筛选的过程。
关键词: 肿瘤,药物筛选,再生,肌肉减少症,肿瘤抑制剂
Current Drug Targets
Title:The Hippo Pathway as Drug Targets in Cancer Therapy and Regenerative Medicine
Volume: 18 Issue: 4
关键词: 肿瘤,药物筛选,再生,肌肉减少症,肿瘤抑制剂
摘要: Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ) co-operate with numerous transcription factors to regulate gene transcriptions. YAP1 and TAZ are negatively regulated by the tumor suppressive Hippo pathway. In human cancers, the Hippo pathway is frequently deregulated and YAP1 and TAZ escape the inhibition by the Hippo pathway. The upregulation of YAP1 and TAZ induces epithelial-mesenchymal transition and increases drug resistance in cancer cells. TAZ is implicated in cancer stemness. In consequence cancers with hyperactive YAP1 and TAZ are associated with poor clinical prognosis. Inhibitors of YAP1 and TAZ are reasoned to be beneficial in cancer therapy. On the other hand, since YAP1 and TAZ play important roles in the regulation of various tissue stem cells and in tissue repair, activators of YAP1 and TAZ are useful in the regenerative medicine. We discuss the potential application of inhibitors and activators of YAP1 and TAZ in human diseases and review the progress of drug screenings to search for them.
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The Hippo Pathway as Drug Targets in Cancer Therapy and Regenerative Medicine, Current Drug Targets 2017; 18 (4) . https://dx.doi.org/10.2174/1389450117666160112115641
DOI https://dx.doi.org/10.2174/1389450117666160112115641 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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