细胞迁移在肿瘤转移和伤口愈合等过程中都发挥着重要作用。IQGAP1作为一个多结构域的脚手架蛋白被发现参与到了细胞迁移的过程中去，但其是否直接参与到黏着斑动态性的调节当中去还未可知。我们的前期工作揭示了Hax1-EB2复合体对调节黏着斑动态性和细胞迁移上起着至关重要的作用。近期我们又发现Hax1是IQGAP1潜在的相互作用蛋白，因此我们推测Hax1-EB2复合体能通过微管正极末端的运输作用调节IQGAP1在表皮角化细胞中黏着斑的定位及互作，从而调控黏着斑的动态性和细胞的定向迁移。在本课题研究中，我们将综合使用分子、细胞生物学及在体小鼠模型手段，系统深入地研究IQGAP1对小鼠表皮角质细胞细胞迁移和皮肤伤口愈合的影响以及相应的分子调控机制。本研究不仅对IQGAP1在细胞迁移中发挥影响的分子机制有了更深入的探讨，也为我们更好地认识IQGAP1在肿瘤转移中的作用以及靶向治疗奠定了理论基础。

Cell migration is an essential process for developmental morphogenesis, wound healing and tumor metastasis. As a multidomain scaffold protein, IQGAP1 is involved in cell adhesion and migration process. However, it is not clear whether it’s directly participated in regulation of focal adhesion dynamics. We previously indentified that Hax1-EB2 protein complex is critical for regulation of focal adhesion dynamics and cell migration. We recently found that Hax1 is a potential binding partner of IQGAP1 by tandem affinity purification, suggesting that Hax1-EB2 protein complex may modulate IQGAP1 colocalization around the focal adhesion, thus regulate focal adhesion dynamic and cell migration via transportation along the microtubule plus end. In this project, we will utilize methodologies at molecular, cellular and in vivo animal models to systematically investigate three specific aims: 1) Examine effect of IQGAP1 on focal adhesion dynamics in mice keratinocytes; 2) Investigate molecular mechanisms by which IQGAP1 regulates focal adhesion dynamics through interaction with Hax1-EB2 protein complex; 3) Study effect of IQGAP1 on skin wound healing. The project will probe deeper into the mechanism of cell migration and shed lights on developing target therapy in cancer metastasis.