Department of Oncology, University of Torino School of Medicine, 10060 Candiolo, Torino, Italy.
Candiolo Cancer Institute - Fondazione del Piemonte per l'Oncologia (FPO) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 10060 Candiolo, Torino, Italy.
Biochem Soc Trans. 2020 Feb 28;48(1):83-93. doi: 10.1042/BST20190309.
Spatiotemporal control of integrin-mediated cell adhesion to the extracellular matrix (ECM) is critical for physiological and pathological events in multicellular organisms, such as embryonic development, angiogenesis, platelet aggregation, leukocytes extravasation, and cancer cell metastatic dissemination. Regulation of integrin adhesive function and signaling relies on the modulation of both conformation and traffic. Indeed, integrins exist in a dynamic equilibrium between a bent/closed (inactive) and an extended/open (active) conformation, respectively endowed with low and high affinity for ECM ligands. Increasing evidence proves that, differently to what hypothesized in the past, detachment from the ECM and conformational inactivation are not mandatory for integrin to get endocytosed and trafficked. Specific transmembrane and cytosolic proteins involved in the control of ECM proteolytic fragment-bound active integrin internalization and recycling exist. In the complex masterplan that governs cell behavior, active integrin traffic is key to the turnover of ECM polymers and adhesion sites, the polarized secretion of endogenous ECM proteins and modifying enzymes, the propagation of motility and survival endosomal signals, and the control of cell metabolism.
整合素介导的细胞与细胞外基质（ECM）的黏附的时空控制对于多细胞生物中的生理和病理事件至关重要，例如胚胎发育、血管生成、血小板聚集、白细胞渗出和癌细胞转移扩散。整合素黏附功能和信号转导的调节依赖于构象和运输的调节。事实上，整合素在弯曲/关闭（失活）和延伸/开放（激活）构象之间存在动态平衡，分别对 ECM 配体具有低亲和性和高亲和性。越来越多的证据证明，与过去假设的不同，从 ECM 上脱离和构象失活并不是整合素被内吞和运输所必需的。存在参与控制 ECM 蛋白水解片段结合的活性整合素内化和再循环的特定跨膜和胞质蛋白。在控制细胞行为的复杂总体计划中，活性整合素运输是 ECM 聚合物和黏附位点周转、内源性 ECM 蛋白和修饰酶的极化分泌、运动和存活内体信号的传播以及细胞代谢控制的关键。
