PDF(Pubmed)
Abstract：
Breast cancer (BC) is the most common type of cancer in women, and remains one of the major causes of death in women worldwide. It is now well established that alterations in membrane trafficking are implicated in BC progression. Indeed, membrane trafficking pathways regulate BC cell proliferation, migration, invasion, and metastasis. The 22 members of the ADP-ribosylation factor (ARF) and the >60 members of the rat sarcoma (RAS)-related in brain (RAB) families of small GTP-binding proteins (GTPases), which belong to the RAS superfamily, are master regulators of membrane trafficking pathways. ARF-like (ARL) subfamily members are involved in various processes, including vesicle budding and cargo selection. Moreover, ARFs regulate cytoskeleton organization and signal transduction. RABs are key regulators of all steps of membrane trafficking. Interestingly, the activity and/or expression of some of these proteins is found dysregulated in BC. Here, we review how the processes regulated by ARFs and RABs are subverted in BC, including secretion/exocytosis, endocytosis/recycling, autophagy/lysosome trafficking, cytoskeleton dynamics, integrin-mediated signaling, among others. Thus, we provide a comprehensive overview of the roles played by ARF and RAB family members, as well as their regulators in BC progression, aiming to lay the foundation for future research in this field. This research should focus on further dissecting the molecular mechanisms regulated by ARFs and RABs that are subverted in BC, and exploring their use as therapeutic targets or prognostic markers.
摘要：
乳腺癌（BC）是女性最常见的癌症类型，并且仍然是全世界妇女死亡的主要原因之一。现在已经确定，膜运输的改变与BC的进展有关。的确,膜运输途径调节BC细胞增殖，迁移,入侵,和转移。ADP-核糖基化因子（ARF）的22个成员和大鼠肉瘤（RAS）相关的脑小GTP结合蛋白（GTPases）家族的>60个成员，属于RAS超家族，是膜贩运途径的主要调控者。类ARF（ARL）亚家族成员参与各种过程，包括囊泡出芽和货物选择。此外，ARFs调节细胞骨架组织和信号转导。RAB是膜贩运所有步骤的关键监管机构。有趣的是,发现这些蛋白质中的一些的活性和/或表达在BC中失调。这里,我们回顾了ARF和RAB监管的过程在公元前是如何被颠覆的，包括分泌/胞吐，内吞作用/再循环，自噬/溶酶体贩运，细胞骨架动力学，整合素介导的信号，在其他人中。因此，我们全面概述了ARF和RAB家庭成员所扮演的角色，以及他们在BC进展中的监管机构，旨在为该领域未来的研究奠定基础。这项研究应该集中在进一步剖析在BC中被颠覆的ARFs和RABs调节的分子机制。并探索它们作为治疗靶标或预后标志物的用途。
