Calcium channel TRPV6 upregulation is associated with poor prognosis of breast cancer by promoting invasion and metastasis, and TRPV6 is a potential target for breast cancer therapy. However, the mechanism by which TRPV6 promotes breast metastasis remains unclear. Here, we report that TRPV6 expression is upregulated in metastatic breast cancers and that TRPV6 overexpression or upregulation accelerates primary breast cancer cell migration. In contrast, TRPV6 suppression decreases cell migration. Mechanistically, TRPV6 activates NFATC2 by increasing NFATC2IP phosphorylation at Ser204, and CDK5 is a candidate kinase that may perform this phosphorylation. Consequently, activated NFATC2 increases breast cancer metastasis by upregulating ADAMTS6 expression. These observations suggest that TRPV6 increases NFATC2 transcriptional activity by increasing NFATC2IP phosphorylation, which consequently upregulates ADAMTS6 expression to promote breast cancer metastasis.
基金：
Ministry of Science and Technology of China (2018YFC1313205), the Shanghai Committee of Science and Technology (11DZ2260200) and the National Natural Science Foundation of China (82073040) (81872342) to Dr. Mi.
第一作者机构：[1]Shanghai Jiao Tong Univ, Tongren Hosp, Basic Med Inst,Minist Educ, Hongqiao Int Inst Med,Sch Med,Key Lab Cell Differ, Shanghai 200025, Peoples R China[2]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Lab Med, Jiading Branch,Sch Med, Shanghai, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Jiao Tong Univ, Tongren Hosp, Basic Med Inst,Minist Educ, Hongqiao Int Inst Med,Sch Med,Key Lab Cell Differ, Shanghai 200025, Peoples R China[2]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Lab Med, Jiading Branch,Sch Med, Shanghai, Peoples R China[4]Shandong Univ, Shandong Acad Med Sci, Dept Radiat Oncol, Shandong Canc Hosp, Jinan 250117, Shandong, Peoples R China[*1]Department of Biochemistry and Molecular Cell Biology[*2]Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China.
推荐引用方式(GB/T 7714)：
Xu Xiang,Li Na,Wang Yugang,et al.Calcium channel TRPV6 promotes breast cancer metastasis by NFATC2IP[J].CANCER LETTERS.2021,519:150-160.doi:10.1016/j.canlet.2021.07.017.
APA：
Xu, Xiang,Li, Na,Wang, Yugang,Yu, Jinming&Mi, Jun.(2021).Calcium channel TRPV6 promotes breast cancer metastasis by NFATC2IP.CANCER LETTERS,519,
MLA：
Xu, Xiang,et al."Calcium channel TRPV6 promotes breast cancer metastasis by NFATC2IP".CANCER LETTERS 519.(2021):150-160
医学