YAP1 and its fusion proteins in cancer initiation, progression and therapeutic resistance.
YAP1 and its fusion proteins in cancer initiation, progression and therapeutic resistance.
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DOI：
10.1016/j.ydbio.2020.12.018
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发表时间：
2021-07
影响因子：
2.7
通讯作者：
Vasioukhin V
中科院分区：
文献类型：
--
作者：
Szulzewsky F;Holland EC;Vasioukhin V
YAP 1是一种转录共激活因子，其活性受Hippo信号通路控制。除了在正常组织稳态和再生中的重要功能外，YAP 1在癌症起始、侵袭性、转移和治疗抗性中也具有突出功能。在这篇综述中，我们讨论了YAP 1的分子功能及其在癌症中的作用，重点是人类癌症中YAP 1活性失调的不同机制，包括Hippo通路上游肿瘤抑制因子的失活，交叉通路，miRNA和病毒癌基因的调节。我们还讨论了最近发现的YAP 1基因融合家族的功能和生物学的新发现，这些基因融合构成了一种新型的YAP 1激活突变，并且可能是几种人类癌症亚型中的致癌驱动因素。最后，我们还讨论了YAP 1功能的治疗性抑制的不同策略。
YAP1 is a transcriptional co-activator whose activity is controlled by the Hippo signaling pathway. In addition to important functions in normal tissue homeostasis and regeneration, YAP1 has also prominent functions in cancer initiation, aggressiveness, metastasis, and therapy resistance. In this review we are discussing the molecular functions of YAP1 and its roles in cancer, with a focus on the different mechanisms of de-regulation of YAP1 activity in human cancers, including inactivation of upstream Hippo pathway tumor suppressors, regulation by intersecting pathways, miRNAs, and viral oncogenes. We are also discussing new findings on the function and biology of the recently identified family of YAP1 gene fusions, that constitute a new type of activating mutation of YAP1 and that are the likely oncogenic drivers in several subtypes of human cancers. Lastly, we also discuss different strategies of therapeutic inhibition of YAP1 functions.
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