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Motin 家族蛋白在肿瘤发生中的作用——最新进展。

The role of Motin family proteins in tumorigenesis-an update.

机构信息

Department of Molecular Oncology, Cancer Biology Evolution Program, H. Lee Moffitt Cancer Center, Tampa, FL, USA.

出版信息

Oncogene. 2023 Apr;42(16):1265-1271. doi: 10.1038/s41388-023-02677-8. Epub 2023 Mar 27.

Abstract

The Motin protein family consists of three members: AMOT (p80 and p130 isoforms), AMOT-like protein 1 (AMOTL1), and AMOT-like protein 2 (AMOTL2). The family members play an important role in processes such as cell proliferation, migration, angiogenesis, tight junction formation, and cell polarity. These functions are mediated through the involvement of the Motins in the regulation of different signal transduction pathways, including those regulated by small G-proteins and the Hippo-YAP pathway. One of the more characterized aspects of Motin family function is their role in regulating signaling through the Hippo-YAP pathway, and while some studies suggest a YAP-inhibitory function other studies indicate the Motins are required for YAP activity. This duality is also reflected in previous reports, often contradictory, that suggest the Motin proteins can function as oncogenes or tumor suppressors in tumorigenesis. In this review we summarize recent findings and integrate that with the existing work describing the multifunctional role of the Motins in different cancers. The emerging picture suggests that the Motin protein function is cell-type and context dependent and that further investigation in relevant cell types and whole organism models is required for the elucidation of the function of this protein family.

摘要

Motin 蛋白家族由三个成员组成:AMOT(p80 和 p130 同工型)、AMOT 样蛋白 1(AMOTL1)和 AMOT 样蛋白 2(AMOTL2)。家族成员在细胞增殖、迁移、血管生成、紧密连接形成和细胞极性等过程中发挥重要作用。这些功能是通过 Motins 参与调节不同信号转导途径来介导的,包括受小分子 G 蛋白和 Hippo-YAP 途径调节的途径。Motin 家族功能的一个更具特征的方面是它们在调节 Hippo-YAP 途径信号中的作用,尽管一些研究表明 Motin 具有抑制 YAP 的功能,但其他研究表明 Motin 对于 YAP 活性是必需的。这种双重性也反映在以前的报告中,这些报告常常相互矛盾,表明 Motin 蛋白在肿瘤发生中可以作为癌基因或肿瘤抑制因子发挥作用。在这篇综述中,我们总结了最近的发现,并将其与描述 Motin 在不同癌症中多功能作用的现有工作相结合。新出现的情况表明,Motin 蛋白的功能是细胞类型和上下文依赖性的,需要在相关细胞类型和全生物体模型中进行进一步研究,以阐明该蛋白家族的功能。

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