在上一个国家基金课题研究中，我们发现肝癌细胞SOCC通道介导的胞外Ca2+内流可促进肝癌细胞内钙信号重构，进而促进其增殖和迁移。前期预实验结果提示，IP3R受体结合蛋白IRBIT作为一种新型的Ca2+负向调节因子,在肝癌组织及细胞中低表达；过表达IRBIT能显著抑制肝癌细胞的增殖与迁移；并且，活化的IRBIT抑制了SOCC介导的胞外Ca2+内流。Co-IP发现活化的IRBIT可与膜上的Orai1通道相结合，加入IRBIT磷酸化阻断剂后此结合消失，提示IRBIT磷酸化是调控IRBIT与Oria1结合、抑制Ca2+内流的关键。本课题拟采用激光共聚焦，膜片钳、荧光共振能量转移、生物信息学预测、动物模型以及GST-pull down等技术，从分子及功能机制阐明IRBIT在肝癌发展中的重要作用，以期为以IRBIT为靶点的肝癌防治提供理论依据。

Granted by our previous NSFC, we have demonstrated that liver tumor cells-SOCC channel is an evolutionarily regulator of cellular calcium homeostasis,facilitated the proliferation and migartion of tumor cells. In line with thefinding, we hypothesized that IRBIT, functioning as the emerging negativeregulator of IP3 receptor thereby limiting the ca homeostasis, could in turn play a suppressive role on tumor development. Our pilot study showing the expression level of IRBIT was attenuated both in tumor tissues and cancer cell lines. Consistently, gain of function in cancer cells significantly suppressed the tumor behaviors in terms of proliferation and migration in vitro. Further, we also found IRBIT negatively regulate SOOC mediated calcium influx, confirming its role on calcium homeostasis. The mechanism of the regulation could be connected with Orai1, one regulator of SOOC, since we found at the plasma membrane, IRBIT could functionally interacted with Orai1 in an IRBIT phosphorylation-dependent manner. Based on above hypothesis, this study will illustrate IRBIT's important role in hepatic cancer through molecular and functional mechanism using laser confocal, patch clamp, FRET, bioinformatics prediction, animal model building and GST-pull down, which will provide a new theoretical basis for intervening hepatic cancer through targeting IRBIT.