Suppr超能文献

RAS 癌基因在控制上皮力学中的作用。

The role of RAS oncogenes in controlling epithelial mechanics.

机构信息

Medical Research Council Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.

Medical Research Council Laboratory for Molecular Cell Biology, University College London, London, WC1E 6BT, UK.

出版信息

Trends Cell Biol. 2023 Jan;33(1):60-69. doi: 10.1016/j.tcb.2022.09.002. Epub 2022 Sep 27.

Abstract

Mutations in RAS are key oncogenic drivers and therapeutic targets. Oncogenic Ras proteins activate a network of downstream signalling pathways, including extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K), promoting cell proliferation and survival. However, there is increasing evidence that RAS oncogenes also alter the mechanical properties of both individual malignant cells and transformed tissues. Here we discuss the role of oncogenic RAS in controlling mechanical cell phenotypes and how these mechanical changes promote oncogenic transformation in single cells and tissues. RAS activation alters actin organisation and actomyosin contractility. These changes alter cell rheology and impact mechanosensing through changes in substrate adhesion and YAP/TAZ-dependent mechanotransduction. We then discuss how these changes play out in cell collectives and epithelial tissues by driving large-scale tissue deformations and the expansion of malignant cells. Uncovering how RAS oncogenes alter cell mechanics will lead to a better understanding of the morphogenetic processes that underlie tumour formation in RAS-mutant cancers.

摘要

RAS 突变是关键的致癌驱动因素和治疗靶点。致癌 Ras 蛋白激活下游信号通路网络,包括细胞外信号调节激酶(ERK)和磷脂酰肌醇 3-激酶(PI3K),促进细胞增殖和存活。然而,越来越多的证据表明,RAS 癌基因也改变了单个恶性细胞和转化组织的机械性能。在这里,我们讨论致癌 RAS 在控制机械细胞表型中的作用,以及这些机械变化如何促进单细胞和组织中的致癌转化。RAS 激活改变肌动蛋白组织和肌球蛋白收缩性。这些变化通过改变基质附着和 YAP/TAZ 依赖性机械转导来改变细胞流变性并影响机械感觉。然后,我们讨论了这些变化如何通过驱动大规模组织变形和恶性细胞的扩张,在细胞群体和上皮组织中发挥作用。揭示 RAS 癌基因如何改变细胞力学将有助于更好地理解 RAS 突变癌症中肿瘤形成的形态发生过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf6a/9850021/88c2547a6cfc/gr1.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验