INSERM UMR1037-Cancer Research Center of Toulouse, Toulouse, France.
Oncogene. 2011 Jun 16;30(24):2697-706. doi: 10.1038/onc.2011.27. Epub 2011 Feb 21.
Dynamic interactions between cells and extracellular matrix (ECM) through integrins influence most cellular functions. Normal cells, but even more, tumor cells are subjected to different forms of stress, including ischemia, radical oxygen species production, starvation, mechanical stress or genotoxic insults due to anti-cancer drugs or irradiation. In these situations, an adaptative cellular response occurs, integrating a complex network of intracellular signaling modules, which, depending on stress intensity, may result to either damage repair followed by complete restitution of cellular functions, or programmed cell death. Because of its implication in oncogenesis and anti-cancer therapy, cellular stress response has been thoroughly investigated. However, most of these studies have been performed in the context of isolated cells without taking into consideration that most cells are part of the tissue within which they interact with ECM through integrin. Few studies have described the influence of stress on cell-to-ECM interaction. However, one can speculate that, in these conditions, cells could functionally interact with protein microenvironment either to create positive interactions to survive (for example by facilitating protective pathways) or negative interaction to die (for example by facilitating detachment). In this review, we summarize the knowledge relative to the influence of different stress modalities on ECM remodeling, integrin expression and/or function modifications, and possible functional consequences, independently from the cellular model as these findings came from a large variety of cells (mesenchymal, endothelial, muscular, epithelial and glandular) and fields of application (cancer, vascular biology and tissue engineering). Most studies support the general notion that non-lethal stress favors ECM stiffness, integrin activation and enhanced survival. This field opens large perspectives not only in tumor biology but also in anti-cancer therapy by targeting one or several steps of the integrin-mediated signaling pathway, including integrin ligation, or activation of integrin-linked enzymes or integrin adaptors.
细胞与细胞外基质（ECM）之间通过整合素的动态相互作用影响大多数细胞功能。正常细胞，甚至更多的肿瘤细胞，都会受到不同形式的压力，包括缺血、活性氧物质的产生、饥饿、机械压力或由于抗癌药物或辐射引起的遗传毒性损伤。在这些情况下，会发生适应性细胞反应，整合细胞内信号模块的复杂网络，根据压力强度，这可能导致细胞功能完全恢复的损伤修复，或程序性细胞死亡。由于其在肿瘤发生和抗癌治疗中的作用，细胞应激反应已经得到了深入研究。然而，大多数这些研究都是在孤立细胞的背景下进行的，没有考虑到大多数细胞都是组织的一部分，它们通过整合素与 ECM 相互作用。很少有研究描述了应激对细胞与 ECM 相互作用的影响。然而，可以推测，在这些条件下，细胞可以与蛋白质微环境进行功能性相互作用，以产生生存的积极相互作用（例如，通过促进保护途径）或死亡的消极相互作用（例如，通过促进分离）。在这篇综述中，我们总结了不同应激模式对 ECM 重塑、整合素表达和/或功能修饰的影响及其可能的功能后果的知识，而不考虑细胞模型，因为这些发现来自于各种不同的细胞（间充质、内皮、肌肉、上皮和腺体）和应用领域（癌症、血管生物学和组织工程）。大多数研究支持这样一种普遍观点，即非致死性应激有利于 ECM 硬度的增加、整合素的激活和生存能力的提高。这一领域不仅在肿瘤生物学方面，而且在通过靶向整合素介导的信号通路的一个或多个步骤，包括整合素连接、整合素连接酶或整合素接头的激活，来进行抗癌治疗方面，都有很大的前景。
