Madrazo Elena, Conde Andrea Cordero, Redondo-Muñoz Javier
Section of Immuno-oncology, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain.
Department of Immunology, Hospital 12 de Octubre Health Research Institute (imas12), Complutense University School of Medicine, 28040 Madrid, Spain.
Cancers (Basel). 2017 Jul 6;9(7):82. doi: 10.3390/cancers9070082.
Cancer cell migration is a complex process that requires coordinated structural changes and signals in multiple cellular compartments. The nucleus is the biggest and stiffest organelle of the cell and might alter its physical properties to allow cancer cell movement. Integrins are transmembrane receptors that mediate cell-cell and cell-extracellular matrix interactions, which regulate numerous intracellular signals and biological functions under physiological conditions. Moreover, integrins orchestrate changes in tumor cells and their microenvironment that lead to cancer growth, survival and invasiveness. Most of the research efforts have focused on targeting integrin-mediated adhesion and signaling. Recent exciting data suggest the crucial role of integrins in controlling internal cellular structures and nuclear alterations during cancer cell migration. Here we review the emerging role of integrins in nuclear biology. We highlight increasing evidence that integrins are critical for changes in multiple nuclear components, the positioning of the nucleus and its mechanical properties during cancer cell migration. Finally, we discuss how integrins are integral proteins linking the plasma membrane and the nucleus, and how they control cell migration to enable cancer invasion and infiltration. The functional connections between these cell receptors and the nucleus will serve to define new attractive therapeutic targets.
癌细胞迁移是一个复杂的过程,需要多个细胞区室进行协调的结构变化和信号传递。细胞核是细胞中最大且最坚硬的细胞器,可能会改变其物理特性以促进癌细胞移动。整合素是介导细胞间和细胞与细胞外基质相互作用的跨膜受体,在生理条件下调节众多细胞内信号和生物学功能。此外,整合素还协调肿瘤细胞及其微环境的变化,这些变化会导致癌症的生长、存活和侵袭性。大多数研究工作都集中在靶向整合素介导黏附和信号传递上。最近令人兴奋的数据表明,整合素在癌细胞迁移过程中控制细胞内部结构和细胞核改变方面起着关键作用。在此,我们综述整合素在核生物学中的新作用。我们强调越来越多的证据表明,整合素对于癌细胞迁移过程中多个核成分的变化、细胞核的定位及其力学特性至关重要。最后,我们讨论整合素如何作为连接质膜和细胞核的整合蛋白,以及它们如何控制细胞迁移以实现癌症的侵袭和浸润。这些细胞受体与细胞核之间的功能联系将有助于确定新的有吸引力的治疗靶点。