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胶质瘤中的河马信号通路。

Hippo Signaling Pathway in Gliomas.

作者信息

Masliantsev Konstantin, Karayan-Tapon Lucie, Guichet Pierre-Olivier

机构信息

Inserm U1084, Laboratoire de Neurosciences Expérimentales et Cliniques, F-86073 Poitiers, France.

Université de Poitiers, F-86073 Poitiers, France.

出版信息

Cells. 2021 Jan 18;10(1):184. doi: 10.3390/cells10010184.

Abstract

The Hippo signaling pathway is a highly conserved pathway involved in tissue development and regeneration that controls organ size through the regulation of cell proliferation and apoptosis. The core Hippo pathway is composed of a block of kinases, MST1/2 (Mammalian STE20-like protein kinase 1/2) and LATS1/2 (Large tumor suppressor 1/2), which inhibits nuclear translocation of YAP/TAZ (Yes-Associated Protein 1/Transcriptional co-activator with PDZ-binding motif) and its downstream association with the TEAD (TEA domain) family of transcription factors. This pathway was recently shown to be involved in tumorigenesis and metastasis in several cancers such as lung, breast, or colorectal cancers but is still poorly investigated in brain tumors. Gliomas are the most common and the most lethal primary brain tumors representing about 80% of malignant central nervous system neoplasms. Despite intensive clinical protocol, the prognosis for patients remains very poor due to systematic relapse and treatment failure. Growing evidence demonstrating the role of Hippo signaling in cancer biology and the lack of efficient treatments for malignant gliomas support the idea that this pathway could represent a potential target paving the way for alternative therapeutics. Based on recent advances in the Hippo pathway deciphering, the main goal of this review is to highlight the role of this pathway in gliomas by a state-of-the-art synthesis.

摘要

河马信号通路是一条高度保守的通路,参与组织发育和再生,通过调节细胞增殖和凋亡来控制器官大小。核心河马通路由一组激酶组成,即MST1/2(哺乳动物STE20样蛋白激酶1/2)和LATS1/2(大肿瘤抑制因子1/2),它们抑制YAP/TAZ(Yes相关蛋白1/含PDZ结合基序的转录共激活因子)的核转位及其与TEAD(TEA结构域)转录因子家族的下游结合。最近发现该通路参与了肺癌、乳腺癌或结直肠癌等多种癌症的肿瘤发生和转移,但在脑肿瘤中的研究仍很少。胶质瘤是最常见且最致命的原发性脑肿瘤,约占恶性中枢神经系统肿瘤的80%。尽管有密集的临床方案,但由于系统性复发和治疗失败,患者的预后仍然很差。越来越多的证据表明河马信号在癌症生物学中的作用,以及恶性胶质瘤缺乏有效的治疗方法,支持了该通路可能代表一个潜在靶点,为替代疗法铺平道路的观点。基于河马通路解析的最新进展,本综述的主要目标是通过最新的综合分析来突出该通路在胶质瘤中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcd6/7831924/3e077ddcfb76/cells-10-00184-g001.jpg

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