癌症是严重威胁人类健康的疾病之一，而肿瘤转移是造成癌症患者死亡的首要原因。肿瘤转移是癌细胞病理性迁移的过程，被称之为“致命迁移”。钙离子作为细胞内最重要的第二信使，多方面的参与调控肿瘤转移过程，然而钙信号本身的特征机制尚未明确。申请人早期以成纤维细胞为模式细胞，发现富集于迁移细胞前沿的“钙闪烁”信号，确立了产生钙闪烁的通道蛋白，并证明钙闪烁起着掌控细胞迁移的“方向舵”作用。相关研究成果拓展了钙信号对复杂生物学过程的整合调控作用，并为疾病研究提供了新的角度和思路，已被众多实验室所接受并广泛应用于肿瘤细胞迁移研究。本项目中，申请人拟以钙信号特性和发放模式为切入点，对肿瘤转移进行从分子到在体的系统性研究，揭示调控肿瘤转移的新基因和新机制。此研究将加深人们对钙信号调控网络的理解，有助于找寻遏制肿瘤转移的新措施，更有望为研发抗癌药物提供新的靶点。

Cancer is one of the most serious diseases that threat to human health. In cancer patients, cancer metastasis is the leading cause of death. Cancer metastasis mainly refers to pathological migration process of tumor cells, which is known as "fatal migration". As the most important second messenger in cells, calcium is involved in the regulation of tumor metastasis in many aspects. However, the characteristic and mechanism of calcium signaling itself has not yet been clarified. By using fibroblasts as the model cells, we previously revealed that the “calcium flickers” enriched in the leading edge of a migrating cell. Further study discovered the key calcium channels that responded to generate calcium flickers and established that calcium flickers played an important role in steering cell migration. Relevant research results extend the integrated regulating functions of calcium signaling on complex biological processes, and provide new perspectives and ideas for disease research, which have been accepted by many laboratories and widely used in cancer cell migration research. In this project, based on the characteristics and release mode of calcium signaling, we conduct a systematic study of cancer metastasis from molecular to in vivo, and to reveal new genes and mechanisms regulating cancer metastasis. Those studies will enhance our understanding of calcium signaling regulatory network, help to find new measures to curb cancer metastasis, and hopefully provide new targets for research and development of anticancer drugs.