PhYsiological function of focal adiesion protein vinexin

细胞迁移在各种生理和病理生理条件下发挥重要作用，包括伤口愈合、血管生成和肿瘤侵袭。阐明细胞迁移的机制有助于开发新的抗癌或抗转移药物。本研究利用vinexin敲除小鼠和敲除细胞，研究了一种新的局灶黏附蛋白vinexin在伤口愈合、细胞迁移和信号转导中的功能。1)创面愈合：我们发现vinexin基因破坏可导致皮肤损伤创面延迟愈合。在体外培养的角质形成细胞中，vinexin表达下调表明vinexin通过调节EGRR2的激活和定位来调节创面愈合。我们发现vinexin抑制ERK的失活。我们还发现，ERK激活的锚定依赖性调节部分取决于失活过程。3)在高侵袭HT1080细胞中vinexin表达的调控细胞骨架和扩散的作用表明vinexin通过控制小g蛋白的激活来调控细胞扩散。我们还发现vinexin直接与小G蛋白的下游因子WAVE2结合，并调节其磷酸化和数量。

Cell migration play important roles in various physiological and pathophysiological conditions, including wound healing, angiogenesis, and tumor invasion. Clarifying the mechanisms of cell migration can contribute to the development of new anti-cancer or anti-metastasis drugs. This research has investigated the function of a novel focal adhesion protein, vinexin, in wound healings, cell migration, and signal transduction,using vinexin-knock out mice and knockdown cells.1) Wound healing-We found that gene disruption of vinexin induces the delayed wound healing of cutaneous injury. Knockdown of vinexin expression in cultured keratinocytes showed that vinexin regulate wound healing through regulating the activation and localization of EGRR2) Anchorage-dependence of signaling-Mechanisms of regulating anchorage-independent activation of ERK by vinexin was examined. We found that vinexin inhibits the inactivation of ERK. We also showed that anchorage-dependent regulation of ERK activation depends on the inactivation process in part.3) Roles in the regulation of cytoskeleton and spreading-Knockdown of vinexin expression in Highly invasive HT1080 cells showed that vinexin has roles in cell spreading through the control of a small G-protein activation. We also found that vinexin directly associates with WAVE2, a downstream factor of the small G protein, and regulates its phosphorylation and amount.