天冬酰胺内肽酶对β3整合素介导的乳腺癌转移的调控及机制研究
结题报告
批准号:
31970702
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
林昶东
学科分类:
细胞极性与细胞运动
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
林昶东
国基评审专家1V1指导 中标率高出同行96.8%
结合最新热点,提供专业选题建议
深度指导申报书撰写,确保创新可行
指导项目中标800+,快速提高中标率
客服二维码
微信扫码咨询
中文摘要
乳腺癌是女性第一高发恶性肿瘤,其较强的远端转移能力是患者生存率低的重要因素。肿瘤细胞转移需要外界环境因子与其表面细胞黏附分子整合素的协同作用,但人们对其机制了解非常有限。本项目针对肿瘤转移这一科学问题,研究影响乳腺癌转移的关键因子并探究其分子机制。我们已发现天冬酰胺内肽酶(asparagine endopeptidase, AEP)在乳腺癌细胞中高表达,并且促进癌细胞的迁移和侵袭。癌细胞分泌到胞外的AEP可通过其RGD序列结合β3整合素;破坏AEP与β3整合素的结合可显著抑制肿瘤细胞的转移。本项目将深入研究AEP与β3整合素相互作用的分子基础,揭示促进肿瘤转移的相关信号通路并在小鼠中验证其功能。筛选抑制AEP与β3整合素结合的抗体,在小鼠肿瘤转移模型中验证该抗体对乳腺癌转移的抑制效果。以上研究将揭示AEP通过β3整合素调控乳腺癌转移的新机制,并为临床治疗乳腺癌转移提供新靶标和候选抗体药物。
英文摘要
Breast cancer is the most malignant tumor of women in the world. Its strong distal metastasis is one of the crucial factors that lead to a low survival rate of the patients. The metastasis of tumor relys on the synergistic effect of external environment factors and integrins, which are cell adhesion molecules expressed on the surface of cancer cells. However, the mechanism is poorly understood. This project will focus on the topic of tumor metastasis. We will study the key factors that affect the metastasis of breast cancer and try to explore the molecular mechanism. At present, we have found that asparagine endopeptidase (AEP) is highly expressed in breast cancer cells, which can promote migration and invasion of cancer cells. Further studies show that extracellular AEP secreted by cancer cells can bind to β3 integrin through its RGD motif. Disruption of AEP-β3 integrin interaction could significantly inhibit the metastasis of cancer cells. We will further study the molecular basis of the interaction of AEP and β3 integrin, explore the downstream signal pathway that promotes tumor metastasis and verify its function in mice. Furthermore, we will screen the blocking antibodies to destroy the binding of AEP and β3 integrin and verify the inhibition effect on the metastasis of breast cancer in mice models. Our research will reveal a new mechanism of AEP in regulating the metastasis of breast cancer through β3 integrin, and provide new targets and candidate antibody drugs for clinical treatment of breast cancer patients.
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:--
发表时间:2021
期刊:生命的化学
影响因子:--
作者:李悦;林昶东
通讯作者:林昶东
DOI:10.1038/s41401-023-01071-0
发表时间:2023
期刊:Acta Pharmacologica Sinica
影响因子:--
作者:YunZhe Zheng;ZhaoYuan Liu;Yue Li;XiaoYing Lv;Yi Wu;MengWen Huang;XingChao Pan;JianFeng Chen;ChangDong Lin
通讯作者:ChangDong Lin
DOI:10.1016/j.xpro.2021.100720
发表时间:2021-09-17
期刊:STAR protocols
影响因子:--
作者:Lin C;Liu Z;Li Y;Chen J
通讯作者:Chen J
DOI:10.1038/s41392-021-00582-8
发表时间:2021
期刊:Signal Transduction and Targeted Therapy
影响因子:39.3
作者:Shu Wang;ChangDong Lin;Yue Li;ZhaoYuan Liu;JunLei Wang;YouHua Zhang;ZhanJun Yan;YueBin Zhang;GuoHui Li;JianFeng Chen
通讯作者:JianFeng Chen
DOI:10.1038/s41423-021-00684-x
发表时间:2021-06
期刊:Cellular & molecular immunology
影响因子:24.1
作者:Yuan M;Wan Y;Liu C;Li Y;Liu Z;Lin C;Chen J
通讯作者:Chen J
Hsp90-α4整合素信号轴在炎症性肠病中的作用及机制研究
LRP12对整合素α4β1介导的细胞黏附与迁移的调控及机制研究
国内基金
海外基金