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评估 ANKHD1 的分子特性和功能及其在癌症中的作用。

Evaluating the Molecular Properties and Function of ANKHD1, and Its Role in Cancer.

机构信息

Department of Infection, Immunity, and Cardiovascular Disease, The University of Sheffield, Sheffield S10 2RX, UK.

Department of Translational Medicine and Therapeutics, Queen Mary University London, London E1 4NS, UK.

出版信息

Int J Mol Sci. 2023 Aug 16;24(16):12834. doi: 10.3390/ijms241612834.

Abstract

Ankyrin repeat and single KH domain-containing protein 1 (ANKHD1) is a large, scaffolding protein composed of two stretches of ankyrin repeat domains that mediate protein-protein interactions and a KH domain that mediates RNA or single-stranded DNA binding. ANKHD1 interacts with proteins in several crucial signalling pathways, including receptor tyrosine kinase, JAK/STAT, mechanosensitive Hippo (YAP/TAZ), and p21. Studies into the role of ANKHD1 in cancer cell lines demonstrate a crucial role in driving uncontrolled cellular proliferation and growth, enhanced tumorigenicity, cell cycle progression through the S phase, and increased epithelial-to-mesenchymal transition. Furthermore, at a clinical level, the increased expression of ANKHD1 has been associated with greater tumour infiltration, increased metastasis, and larger tumours. Elevated ANKHD1 resulted in poorer prognosis, more aggressive growth, and a decrease in patient survival in numerous cancer types. This review aims to gather the current knowledge about ANKHD1 and explore its molecular properties and functions, focusing on the protein's role in cancer at both a cellular and clinical level.

摘要

锚蛋白重复和单个 KH 结构域蛋白 1(ANKHD1)是一种由两个串联的锚蛋白重复结构域和一个 KH 结构域组成的大型支架蛋白,这些结构域介导蛋白质-蛋白质相互作用和 RNA 或单链 DNA 结合。ANKHD1 与几种关键信号通路中的蛋白质相互作用,包括受体酪氨酸激酶、JAK/STAT、机械敏感 Hippo(YAP/TAZ)和 p21。对癌细胞系中 ANKHD1 作用的研究表明,它在驱动不受控制的细胞增殖和生长、增强肿瘤发生、通过 S 期促进细胞周期进程以及增加上皮-间充质转化方面发挥着关键作用。此外,在临床水平上,ANKHD1 的表达增加与更大的肿瘤浸润、更高的转移和更大的肿瘤相关。在许多癌症类型中,升高的 ANKHD1 导致预后较差、生长更具侵袭性以及患者生存率下降。本综述旨在汇集关于 ANKHD1 的现有知识,并探讨其分子特性和功能,重点关注该蛋白在细胞和临床水平上在癌症中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2b/10454556/dfa3e53045e0/ijms-24-12834-g009.jpg

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