驱动蛋白分子KIF4A影响肿瘤细胞迁移侵袭的分子机制研究

Chromokinesin KIF4A is a motor protein involved in multiple cellular processes including proliferating cell division, protein intracellular trafficking and neuronal survival in brain development. Our previous results showed that KIF4A binds and translocates PRC1 during mitosis to control normal cell division. Thus KIF4A plays important roles in tumorigenesis. We also find that KIF4A plays negative roles on development of clinical gastric cancer as well as proliferatin of gastric tumor cells both in vitro and in vivo. Furthermore, KIF4A also took place negative regulation on metastasis of gastric cancer in clinic. However its fuctions in the process of tumor cell migaration and invasion are still unclear.This study will firstly confirm that chromokinesin KIF4A inhibits migarative and invasive abilities of gastric cancer cell in vitro and then unravel their molecule mechanisms. Mainly, the study will focus on two parts in detail. One is KIF4A's inhibition function on the dynamics of microtublues plus ends in cell leading edge. The other is KIF4A's transportation for an focal adhesion protein, Supervillin (SV), who mainly inhibits formation of focal adhesion during cell migration and invasion. Both of KIF4A's fucntions will negatively regulated process of migaration and invasion of gastric cancer cells. Finally, our study will shed light on the rationale of KIF4A's inhibition on metastasis of clinical cancer and then provide strong evidences for chromokinesin KIF4A serving as one of potent targets for tumor prognostics and treatment in clinic.

染色体驱动蛋白分子KIF4A是一个多功能动力蛋白分子，参与调控细胞有丝分裂、胞内大分子的转运以及神经元发育再生等多个细胞基本生命过程。我们最早报道KIF4A在细胞内结合转运PRC1蛋白，调控细胞正常有丝分裂，因此KIF4A也参与肿瘤的发生过程。同时我们报道KIF4A对胃癌的发生发展以及胃癌细胞的增殖发挥负作用，进一步研究发现KIF4A在临床胃癌的转移过程中同样表现为负调控。但KIF4A在肿瘤细胞迁移侵袭过程中的作用尚不明确。本研究旨在通过确定KIF4A抑制体外培养的胃癌细胞迁移侵袭功能的基础上，深入探讨其潜在分子机制：主要集中在KIF4A对细胞内微管远端（正极）动态不稳定性的抑制作用以及KIF4A对抑制黏着斑形成的Supervillin蛋白分子的细胞内转运两个方面。该研究能帮助人们更好的理解KIF4A在肿瘤转移过程中的作用，为该蛋白应用于肿瘤的诊断、治疗奠定理论基础。

染色体驱动蛋白分子KIF4A是一个多功能动力蛋白分子，参与调控细胞有丝分裂、胞内大分子的转运以及神经元发育再生等多个细胞基本生命过程。我们最早报道KIF4A在细胞内结合转运PRC1蛋白，调控细胞正常有丝分裂，因此KIF4A也参与肿瘤的发生过程。同时我们报道KIF4A对胃癌的发生发展以及胃癌细胞的增殖发挥负作用，进一步研究发现KIF4A在临床胃癌的转移过程中同样表现为负调控。但KIF4A在肿瘤细胞迁移侵袭过程中的作用尚不明确。我们通过确定KIF4A抑制体外培养的胃癌细胞迁移侵袭功能的基础上，深入探讨其潜在分子机制。我们的研究结果表明，KIF4A通过与抑制黏着斑形成的Supervillin蛋白分子相互结合，进而抑制黏着斑形成。该研究能帮助人们更好的理解KIF4A在肿瘤转移过程中的作用，为该蛋白应用于肿瘤的诊断、治疗奠定理论基础。