title: Rap2B promotes proliferation, migration, and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway.
abstract: Rap2B, a member of GTP-binding proteins, is widely upregulated in many types of tumors and promotes migration and invasion of human suprarenal epithelioma. However, the function of Rap2B in breast cancer is unknown. Expression of Rap2B was examined in breast cancer cell lines and human normal breast cell line using Western blot analysis. Using the CCK-8 cell proliferation assay, cell cycle analysis, and transwell migration assay, we also elucidated the role of Rap2B in breast cancer cell proliferation, migration, and invasion. Results showed that the expression of Rap2B is higher in tumor cells than in normal cells. Flow cytometry and Western blot analysis revealed that Rap2B elevates the intracellular calcium level and further promotes extracellular signal-related kinase (ERK) 1/2 phosphorylation. By contrast, calcium chelator BAPTM/AM and MEK inhibitor (U0126) can reverse Rap2B-induced ERK1/2 phosphorylation. Furthermore, Rap2B knockdown inhibits cell proliferation, migration, and invasion abilities via calcium related-ERK1/2 signaling. In addition, overexpression of Rap2B promotes cell proliferation, migration and invasion abilities, which could be neutralized by BAPTM/AM and U0126. Taken together, these findings shed light on Rap2B as a therapeutic target for breast cancer.
authors.affiliation: 1] Cancer Institute, Xuzhou Medical College, Xuzhou 221002, Jiangsu, P.R. China [2] Department of Radiation Oncology and Lineberger Comprehensive Cancer Center, School of Medicine, the University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27514, USA.
authors.forename: Jiehui
authors.initials: J
authors.lastname: Di
authors.affiliation: 1] Cancer Institute, Xuzhou Medical College, Xuzhou 221002, Jiangsu, P.R. China [2] Department of Oncology, the People's Hospital of Kaixian, Kaixian 405400, Chongqing, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou 221002, Jiangsu, P.R. China.
authors.forename: Debao
authors.initials: D
authors.lastname: Qu
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou 221002, Jiangsu, P.R. China.
authors.forename: Juangjuan
authors.initials: J
authors.lastname: Tang
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou 221002, Jiangsu, P.R. China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Cao
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou 221002, Jiangsu, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou 221002, Jiangsu, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou 221002, Jiangsu, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou 221002, Jiangsu, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Bai
authors.affiliation: 1] Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou 221002, Jiangsu, P.R. China [2] Department of Radiation Oncology and Lineberger Comprehensive Cancer Center, School of Medicine, the University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27514, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou 221002, Jiangsu, P.R. China.
authors.forename: Junnian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D020668:rap GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C065562:RAP2B protein, human; D020668:rap GTP-Binding Proteins; D002118:Calcium