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XBP1 在癌症中的新兴作用。

The emerging role of XBP1 in cancer.

机构信息

School of Medicine, Southeast University, Nanjing, 210009, China.

Department of Respiratory, Zhongda Hospital of Southeast University, Nanjing, 210009, China.

出版信息

Biomed Pharmacother. 2020 Jul;127:110069. doi: 10.1016/j.biopha.2020.110069. Epub 2020 Apr 12.

Abstract

X-box binding protein 1 (XBP1) is a unique basic-region leucine zipper (bZIP) transcription factor whose dynamic form is controlled by an alternative splicing response upon disturbance of homeostasis in the endoplasmic reticulum (ER) and activation of the unfolded protein response (UPR). XBP1 was first distinguished as a key regulator of major histocompatibility complex (MHC) class II gene expression in B cells. XBP1 communicates with the foremost conserved signalling component of the UPR and is essential for cell fate determination in response to ER stress (ERS). Here, we review recent advances in our understanding of this multifaceted translation component in cancer. In this review, we briefly discuss the role of XBP1 mediators in the UPR and the transcriptional function of XBP1. In addition, we describe how XBP1 operates as a key factor in tumour progression and metastasis. We mainly review XBP1's expression, function and prognostic value in research on solid tumours. Finally, we discuss multiple approaches, especially those involving XBP1, that overcome the immunosuppressive effect of the UPR in cancer that could potentially be useful as antitumour therapies.

摘要

X 盒结合蛋白 1(XBP1)是一种独特的碱性亮氨酸拉链(bZIP)转录因子,其动态形式受内质网(ER)内稳态干扰和未折叠蛋白反应(UPR)激活时的选择性剪接反应控制。XBP1 最初被鉴定为 B 细胞中主要组织相容性复合物(MHC)II 类基因表达的关键调节因子。XBP1 与 UPR 中最保守的信号成分通讯,是 ER 应激(ERS)响应中细胞命运决定所必需的。在这里,我们回顾了我们对癌症中这种多方面翻译成分的理解的最新进展。在这篇综述中,我们简要讨论了 XBP1 介质在 UPR 中的作用和 XBP1 的转录功能。此外,我们描述了 XBP1 如何作为肿瘤进展和转移的关键因素发挥作用。我们主要综述了 XBP1 在实体瘤研究中的表达、功能和预后价值。最后,我们讨论了多种方法,特别是涉及 XBP1 的方法,这些方法可以克服癌症中 UPR 的免疫抑制作用,作为抗肿瘤疗法可能具有潜在的用途。

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