钙信号负向调节因子IRBIT抑制肝癌细胞恶性生物学行为的分子机制研究

批准号:
31960151
项目类别:
地区科学基金项目
资助金额:
40.0 万元
负责人:
徐靖宇
依托单位:
学科分类:
细胞信号转导
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
徐靖宇
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中文摘要
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。
英文摘要
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.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.3389/fphys.2022.870243
发表时间:2022
期刊:FRONTIERS IN PHYSIOLOGY
影响因子:4
作者:Xiang, Yiwei;Fan, Dongdong;An, Qimin;Zhang, Ting;Wu, Xianli;Ding, Jianhong;Xu, Xiaolin;Yue, Gengyu;Tang, Siqi;Du, Qian;Xu, Jingyu;Xie, Rui
通讯作者:Xie, Rui
DOI:10.3389/fphys.2021.567650
发表时间:2021
期刊:Frontiers in physiology
影响因子:4
作者:Yang X;Lou J;Shan W;Ding J;Jin Z;Hu Y;Du Q;Liao Q;Xie R;Xu J
通讯作者:Xu J
DOI:10.1016/j.yexcr.2022.113227
发表时间:2022-05
期刊:Experimental cell research
影响因子:3.7
作者:Yiwei Xiang;Xiaolin Xu;Ting Zhang;Xianli Wu;Dongdong Fan;Yanxia Hu;Jianhong Ding;Xiaoxu Yang;Jun Lou;Qian Du;Jingyu Xu;R. Xie
通讯作者:Yiwei Xiang;Xiaolin Xu;Ting Zhang;Xianli Wu;Dongdong Fan;Yanxia Hu;Jianhong Ding;Xiaoxu Yang;Jun Lou;Qian Du;Jingyu Xu;R. Xie
The role of Nod-like receptor protein 3 inflammasome activated by ion channels in multiple diseases.
DOI:10.1007/s11010-022-04602-1
发表时间:2023-06
期刊:Molecular and cellular biochemistry
影响因子:4.3
作者:Xu X;Wu X;Yue G;An Q;Lou J;Yang X;Jin Z;Ding J;Hu Y;Du Q;Xu J;Xie R
通讯作者:Xie R
DOI:10.1016/j.pbiomolbio.2022.11.003
发表时间:2022-11
期刊:Progress in biophysics and molecular biology
影响因子:3.8
作者:Ting Zhang;Qi Liu;Zhuo Li;Siqi Tang;Qimin An;Dongdong Fan;Yiwei Xiang;Xianli Wu;Zhe Jin-Zh
通讯作者:Ting Zhang;Qi Liu;Zhuo Li;Siqi Tang;Qimin An;Dongdong Fan;Yiwei Xiang;Xianli Wu;Zhe Jin-Zh
CaSR介导的内质网应激在调控活化肝星状细胞凋亡中的作用及机制研究
- 批准号:81970541
- 项目类别:面上项目
- 资助金额:55.0万元
- 批准年份:2019
- 负责人:徐靖宇
- 依托单位:
钠钙交换体亚型1介导CDX2上调促进Barrett食管发生发展的研究
- 批准号:81660099
- 项目类别:地区科学基金项目
- 资助金额:37.0万元
- 批准年份:2016
- 负责人:徐靖宇
- 依托单位:
肝癌细胞中钙离子信号通路与细胞内PH调节的信号通路快速交互作用的机制研究
- 批准号:81160265
- 项目类别:地区科学基金项目
- 资助金额:50.0万元
- 批准年份:2011
- 负责人:徐靖宇
- 依托单位:
国内基金
海外基金
