微管驱动蛋白Kid调节乳腺癌细胞增殖及其分子机制研究

Kid(kinesin-like DNA binding protein) belongs to the microtubule-dependent motor proteins superfamily, also known as KIF22. Kid protein interacts with microtubule to active its ATPase activity，and plays an important role in mitosis..Studies indicated that many members of kinesin family were closely related to cell alnormal proliferation and tumorgenesis, however the role of Kid protein in tumor remains to be elucidated. In our previous study, we found that Kid protein overexpressed in breast cancer tissues and it can also promote the breast cancer cell proliferation in vitro. In this proposal, we will study the functions of Kid protein in the cell proliferation of breast cancer at cellular level, animal model level and clinical case analysis, respectively. meanwhile, we found that Kid protein interacted with Aurora-B kinase in mitosis whose related to cancer. We will also investigate the possible molecular mechanisms and biological function of the interaction between Kid and Aurora-B, further, we will verify that whether Kid regulates cell proliferation though interacting with Aurora-B..In summary, the in-depth study of Kid protein and its mechanism, would be expected to more understanding of the basic rule of cellular activity，and provide novel ideas for tumor pathogenesis, as well as potential novel target for the treatment of breast cancer.

Kid(kinesin-like DNA binding protein)是微管驱动蛋白Kinesin家族的成员，也称KIF22，结合微管后激活其ATPase活性，在细胞有丝分裂期发挥重要功能。.Kinesin家族的许多成员在细胞异常增殖和肿瘤发生中都起重要的作用，但Kid在这方面的功能还尚未见报道。前期研究发现，Kid在乳腺癌组织中高表达并在体外促进癌细胞生长，故本课题拟在细胞水平、动物模型和临床病例分析三方面系统阐述Kid在乳腺癌细胞增殖中功能。另外我们发现Kid与有丝分裂激酶Aurora-B在细胞内存在相互作用，后者与肿瘤相关，我们将进一步研究其作用的分子机制，及其蛋白质结合所发挥的生物学功能，并探讨Kid是否通过与Aurora-B作用而影响细胞增殖。.对Kid及其作用机制的深入研究，将丰富对细胞生命活动基本规律的认识，为肿瘤发病机制研究提供新的思路，为其治疗提供新的潜在靶点。

Kid(kinesin-like DNA binding protein)是微管驱动蛋白Kinesin家族的成员，也称KIF22，结合微管后激活其ATPase活性，在细胞有丝分裂期发挥作用。Kinesin家族的许多成员在细胞异常增殖和肿瘤发生中都起了重要作用，但Kid在这方面的功能还未见报道。. 在本课题的研究中发现：（1）微管驱动蛋白Kid在乳腺癌组织中表达上调，在体外实验中促进癌细胞生长，体内实验中影响裸鼠成瘤。抑制Kid的表达导致细胞在有丝分裂期阻滞。（2）Kid通过与有丝分裂激酶Aurora-B相互作用，调节细胞有丝分裂进程。Aurora-B激酶活性影响Kid的细胞定位及功能，Kid是Aurora-B激酶的潜在调节底物。Kid的磷酸化水平对其细胞内定位和功能的发挥至关重要。（3）在研究过程中我们发现，有丝分裂激酶Aurora-A可通过磷酸化并激活PLK2，进中心粒的复制，进而调节细胞周期和增殖。. 综上所述，Kid确实调节肿瘤细胞增殖过程。上述实验结果，丰富了我们对于有丝分裂过程和细胞增殖调控过程的理解，加深了对细胞生命活动基本规律的认识，为肿瘤发病规律研究提供了新的思路，为治疗提供了新的潜在靶点。