Metastatic progression is strongly influenced by the connection between hyperactivated signaling pathways. G-protein coupled receptors (GPCRs) through β-arrestins (β-arrs), which serve as intracellular signaling molecules, integrate different pathways to control multiple aspects of metastatic process. As primary component of a core-scaffold, β-arr-dependent signaling represents a mean to direct spatiotemporal specificity of multi-protein complexes in invasion and extracellular matrix (ECM) degradation. Under this paradigm, β-arrs engage a growing number of signaling molecules and organizing protein networks controlling multiple pathways, and cytoskeleton modifications, permitting adaptation to the tumor microenvironment to sustain metastatic dissemination. These findings implicate GPCR/β-arr function as a regulatory tethering hub to orchestrate diverse cellular mechanisms of cancer cell migration and invasion that are critical for metastatic progression. In this chapter, we outline the most recent findings on GPCR/β-arr-guided molecular interactions in specific intracellular compartments to drive metastasis, while discussing new perspectives for the selection of most effective therapeutic options for a personalized medicine.

中文翻译：

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通过GPCR /β-arrestin调节肌动蛋白细胞骨架动力学在癌症侵袭和转移中的新见解。

转移进程受高度激活的信号通路之间的联系的强烈影响。通过β-arrestin（β-arrs）的G蛋白偶联受体（GPCR）作为细胞内信号分子，整合了不同途径来控制转移过程的多个方面。作为核心支架的主要组成部分，依赖于β-arr的信号传导代表了一种手段，可以指导多种蛋白质复合物在侵袭和细胞外基质（ECM）降解中的时空特异性。在这种范式下，β-arrs参与越来越多的信号分子并组织控制多个途径和细胞骨架修饰的蛋白质网络，从而使其适应肿瘤微环境以维持转移性传播。这些发现暗示了GPCR /β-arr作为调节性枢纽枢纽，以协调癌细胞迁移和侵袭的多种细胞机制，这些机制对于转移的进展至关重要。在本章中，我们概述了有关特定细胞内区室中GPCR /β-arr指导的分子相互作用以驱动转移的最新发现，同时讨论了为个性化药物选择最有效治疗方案的新观点。