文章：

每一步：整合素在癌症进展和转移中的作用

Every step of the way: integrins in cancer progression and metastasis

原文发布日期：2018-07-12

DOI: 10.1038/s41568-018-0038-z

类型: Review Article

开放获取: 否

英文摘要：

Cell adhesion to the extracellular matrix is fundamental to tissue integrity and human health. Integrins are the main cellular adhesion receptors that through multifaceted roles as signalling molecules, mechanotransducers and key components of the cell migration machinery are implicated in nearly every step of cancer progression from primary tumour development to metastasis. Altered integrin expression is frequently detected in tumours, where integrins have roles in supporting oncogenic growth factor receptor (GFR) signalling and GFR-dependent cancer cell migration and invasion. In addition, integrins determine colonization of metastatic sites and facilitate anchorage-independent survival of circulating tumour cells. Investigations describing integrin engagement with a growing number of versatile cell surface molecules, including channels, receptors and secreted proteins, continue to lead to the identification of novel tumour-promoting pathways. Integrin-mediated sensing, stiffening and remodelling of the tumour stroma are key steps in cancer progression supporting invasion, acquisition of cancer stem cell characteristics and drug resistance. Given the complexity of integrins and their adaptable and sometimes antagonistic roles in cancer cells and the tumour microenvironment, therapeutic targeting of these receptors has been a challenge. However, novel approaches to target integrins and antagonism of specific integrin subunits in stringently stratified patient cohorts are emerging as potential ways forward.

摘要翻译： 

细胞与细胞外基质的粘附对于组织完整性和人类健康至关重要。整合素作为主要的细胞粘附受体，通过其作为信号分子、机械转导器和细胞迁移机制关键组分的多重作用，参与了从原发性肿瘤发展到转移的癌症进展的几乎所有阶段。肿瘤中常可检测到整合素表达的改变，其在支持致癌生长因子受体信号传导及生长因子受体依赖性癌细胞迁移和侵袭中发挥作用。此外，整合素决定了转移部位的定植，并促进循环肿瘤细胞的锚定非依赖性存活。研究揭示了整合素与日益增多的多功能细胞表面分子（包括通道、受体和分泌蛋白）的相互作用，不断引领着新型促肿瘤通路的发现。整合素介导的肿瘤基质的感知、硬化和重塑是癌症进展的关键步骤，支持侵袭、癌症干细胞特性的获取及耐药性的形成。鉴于整合素的复杂性及其在癌细胞和肿瘤微环境中的适应性和有时拮抗的作用，针对这些受体的治疗一直是一个挑战。然而，靶向整合素的新方法及在严格分层的患者群体中拮抗特定整合素亚基的策略正在成为潜在的前进方向。

原文链接：

Every step of the way: integrins in cancer progression and metastasis