Dugina V B, Shagieva G S, Kopnin P B
A.N. Belozerskiy Research Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Moscow, Russia.
Biological Faculty, M.V. Lomonosov Moscow State University, Moscow, Russia.
Front Pharmacol. 2022 May 26;13:895703. doi: 10.3389/fphar.2022.895703. eCollection 2022.
The cytoplasmic actin isoforms (β- and γ-actins) contribute greatly to cellular processes such as cel-cell and cell-matrix interactions, as well as cell polarization, motility and division. Distinct isoforms modulations are linked to serious pathologies, so investigations of underlying mechanisms would be of major relevance not only for fundamental research but also for clinical applications. Therefore, the study of the relevant mechanisms of change in the isoform's balance is important for basic research and for clinical studies. The disruption of actin cytoskeleton and intercellular adhesions contribute to the neoplastic transformation, as it is important for the tumor growth, invasiveness and metastasis. Cytoplasmic actins display the functional diversity: β-actin is responsible for contractility, whereas γ-actin participates in the submembrane flexible cortex organization and direction cell motility. The involvement of β- and γ-actin in cell architecture, motility, division, and adhesion junctions in normal cells is not equivalent, and the major question was following: whether isoform ratio and the distribution in the cell corresponds to pathological function. Significant data were obtained in the study of tumor and normal cells in culture, as well as on clinical material of human tissues, and via selective regulation of β- and γ-actin's expression. Investigation of the actins' diversity and function in cancers may help to choose the benefit treatment strategies, and to design new therapies.
细胞质肌动蛋白异构体(β-肌动蛋白和γ-肌动蛋白)对细胞间和细胞与基质间的相互作用等细胞过程有很大贡献,同时也参与细胞极化、运动和分裂。不同异构体的调节与严重病理状况相关,因此对其潜在机制的研究不仅对基础研究而且对临床应用都具有重要意义。所以,研究异构体平衡变化的相关机制对基础研究和临床研究都很重要。肌动蛋白细胞骨架和细胞间黏附的破坏有助于肿瘤转化,因为这对肿瘤生长、侵袭和转移很重要。细胞质肌动蛋白表现出功能多样性:β-肌动蛋白负责收缩性,而γ-肌动蛋白参与膜下柔性皮质组织的形成并指导细胞运动。β-肌动蛋白和γ-肌动蛋白在正常细胞的细胞结构、运动、分裂和黏附连接中的参与程度并不相同,主要问题如下:异构体比例及其在细胞中的分布是否与病理功能相对应。通过对培养的肿瘤细胞和正常细胞以及人体组织临床材料的研究,以及通过对β-肌动蛋白和γ-肌动蛋白表达的选择性调节,获得了大量数据。对癌症中肌动蛋白多样性和功能的研究可能有助于选择有益的治疗策略,并设计新的疗法。