新基因CIAPIN1在胃癌转移中的生物学作用及信号转导机制

CIAPIN1 is a newly identified MDR related human gene in gastric cancer, which is also proven to be a downstream effecter of cytokine induced apoptosis in Ras-signaling pathway. In the National Foundation of Natural Sciences funding (NO:30471989, completed), we found that CIAPIN1 could regulate gastric cancer invasion and metastasis. However, the exact molecular mechanism of this gene in gastric cancer metastasis is still unclear. As the role of cell adhesion molecules, matrix degrading enzymes, and cell molecular motility, cancer could occur distant metastasis. Our microarray results show CIAPIN1 could regulate a large of metastasis-related molecules, such as actin, MMP7, Tubulin and Rho signaling molecules. Therefore, this project aim to further investigate the CIAPIN1 regulated molecular mechanism of gastric cancer metastasis, which including adhesion molecules Wnt / E-cadherin pathway, matrix degrading enzymes PI-3K/AKT pathway, and cell molecular motility Rho / Rock pathway, Tubulin assembly pathways, to explore their relationship with gastric cancer metastasis. Finally, we hope to identify the CIAPIN1 regulated moleculal mechanism in gastric cancer metastasis, and ultimately revealed the biofunction of new gene CIAPIN1.

CIAPIN1是一个新的人类胃癌耐药相关基因，也是RAS信号通路下细胞因子诱导凋亡的调控分子之一。在国家自然科学基金资助下（30471989，已结题），我们在国际上首次发现CIAPIN1与胃癌转移密切相关，但其机制尚未阐明。肿瘤转移主要是：粘附分子、蛋白水解酶类、细胞运动分子三类分子共同作用的结果。我们基因芯片结果显示CIAPIN1可调控肿瘤转移调节网络中众多分子的变化，包括：actin,MMP7,Tubulin和Rho信号抑制。因此，本项目拟进一步观察CIAPIN1调控胃癌转移的具体机制，深入探讨粘附分子Wnt/E-cadherin通路，蛋白水解酶PI-3K/AKT通路，以及细胞运动分子Rho/Rock通路、Tubulin组装等四条途径在其中的作用，探讨它们与临床胃癌转移的相关性，以期阐明CIAPIN1调控下的转移分子群在胃癌转移中的作用机制，完善对新基因CIAPIN1功能的认识。