BATF2结合IRF1调控DUSP6转录抑制胃癌侵袭转移的机制研究

肿瘤侵袭转移是影响胃癌患者预后的关键因素，但其潜在分子机制尚未完全阐明。我们前期研究发现BATF2在胃癌组织中呈低表达，且与双特异性磷酸酶DUSP6具有共表达现象。BATF2可与核转录因子IRF1相互结合，我们进一步分析发现DUSP6转录起始区域上可能存在IRF1结合位点。因此，本项目拟在前期研究的基础上采用细胞及分子生物学技术，结合裸鼠胃癌转移模型体内外研究证明如下科学假说，BATF2与IRF1形成蛋白复合体，后者上调DUSP6转录水平，促进ERK的T202/Y204位点去磷酸化，下调基质金属蛋白酶MMP2、MMP9表达从而抑制胃癌侵袭转移。本项目揭示了BATF2抑制胃癌侵袭转移的分子机制，为将基于BATF2的靶向治疗策略应用于胃癌个体化治疗提供理论依据与实验基础。

Tumor invasion and metastasis are the key factors affecting the prognosis of patients with gastric cancer, but the underlying molecular mechanisms have not been fully elucidated. Our previous studies have found that BATF2 was low-expressed in gastric cancer tissues and co-expressed with bispecific phosphatase DUSP6. BATF2 can combine with the nuclear transcription factor IRF1. Our further analysis revealed that there may be IRF1 binding sites on the transcription initiation region of DUSP6. On the basis of previous studies, the present project contributes to testing the following scientific hypothesis in vivo and in vitro by cell and molecular biology techniques, combined with nude mice gastric cancer metastasis model. BATF2 and IRF1 form a protein complex, which up-regulates the transcription level of DUSP6, promotes the dephosphorylation of ERK at T202/Y204 site, and down-regulates the expression of MMP2 and MMP9 of matrix metalloproteinases to inhibit the invasion and metastasis of gastric cancer. This project revealed the molecular mechanisms of BATF2 in inhibiting the invasion and metastasis of gastric cancer, and provided theoretical and experimental basis for the application of BATF2-based targeted therapy strategy in individualized treatment of gastric cancer.