DAB2IP/hnRNPK/MMP2/9信号轴调控结直肠癌细胞侵袭、转移的分子机制

DAB2IP，a novel colorectal carcinoma metastasis-associated protein，was screened from microarray．It was showed that down-regulation of DAB2IP could increase the expression of hnRNPK, MMP2 and MMP9 in our previous study．Based on the bioinformatic analyses and preliminary experiments，we proposed a hypothesis that DAB2IP/ hnRNPK/MMP2/9 signaling axis could regulate invasion and metastasis of colorectal carcinoma cell．In the study， transfection，interference and experiments in vitro and in vivo and so on are performed to validate the hypothesis, to confirm that the expression and subcelluar localization of hnRNPK is regulated by DAB2IP through Ras/MAPK signaling pathway, to prove that MMP2/9 mediates the effect of hnRNPK directly on invasion and metastasis, to test and verify the role of DAB2IP/ hnRNPK /MMP2/9 signaling axis in the progression of colorectal carcinoma．In our study，we aim to reveal a novel regulatory mechanism in colorectal carcinoma and provide a novel theory and gene targets for clinical intervention of invasion and metastasis of colorectal carcinoma.

DAB2IP是我们从芯片中筛选出的一个新的结直肠癌转移相关蛋白。预实验发现，沉默DAB2IP能上调hnRNPK 、MMP2和MMP9的表达。基于预实验和文献检索结果，我们提出DAB2IP/hnRNPK /MMP2/9信号轴调控结直肠癌细胞侵袭、转移的假说。本研究拟用转染、干扰及体内外等实验验证该假说:明确DAB2IP是通过Ras/MAPK通路调控hnRNPK的表达和亚细胞定位；证实MMP2/9直接介导hnRNPK在结直肠癌中的功能；检验DAB2IP/ hnRNPK/MMP2/9在结直肠癌演进调控中的作用。旨在揭示一个新的结直肠癌调控机制，为抗结直肠癌侵袭和转移提供新的理论基础和基因靶点。

DAB2IP是我们从芯片中筛选出的一个新的结直肠癌转移相关蛋白。预实验发现，沉默DAB2IP能上调hnRNPK、MMP2和MMP9的表达。基于预实验和文献检索结果，我们提出DAB2IP/hnRNPK/MMP2/9信号轴调控结直肠癌细胞侵袭、转移的假说。本研究拟用转染、干扰及体内外等实验验证该假说:明确DAB2IP是通过Ras/MAPK通路调控hnRNPK的表达和亚细胞定位；证实MMP2/9直接介导hnRNPK在结直肠癌中的功能；检验DAB2IP/hnRNPK/MMP2/9在结直肠癌演进调控中的作用。旨在揭示一个新的结直肠癌调控机制，为抗结直肠癌侵袭和转移提供新的理论基础和基因靶点。