Rap2B promotes proliferation, migration, and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway.
Rap2B promotes proliferation, migration, and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway.
复制标题
Rap2B通过钙相关ERK1/2信号通路促进人乳腺癌增殖、迁移和侵袭
DOI：
10.1038/srep12363
复制
发表时间：
2015-07-23
影响因子：
4.6
通讯作者：
Zheng J
中科院分区：
文献类型：
--
作者：
Di J;Huang H;Qu D;Tang J;Cao W;Lu Z;Cheng Q;Yang J;Bai J;Zhang Y;Zheng J
Rap 2B是GTP结合蛋白的一员，在许多类型的肿瘤中广泛上调，并促进人肾上腺上皮瘤的迁移和侵袭。然而，Rap 2B在乳腺癌中的功能尚不清楚。采用Western blot分析检测乳腺癌细胞系和人正常乳腺细胞系中Rap 2B的表达。通过CCK-8细胞增殖实验、细胞周期分析和transwell迁移实验，进一步阐明Rap 2B在乳腺癌细胞增殖、迁移和侵袭中的作用。结果显示Rap 2B在肿瘤细胞中的表达高于正常细胞。流式细胞术和Western blot分析显示Rap 2B升高细胞内钙水平，并进一步促进细胞外信号相关激酶（ERK）1/2磷酸化。相反，钙离子螯合剂BAPTM/AM和MEK抑制剂（U 0126）可逆转Rap 2B诱导的ERK 1/2磷酸化。此外，Rap 2B敲低通过钙相关ERK 1/2信号传导抑制细胞增殖、迁移和侵袭能力。此外，Rap 2B的过表达促进了细胞的增殖、迁移和侵袭能力，这可以被BAPTM/AM和U 0126中和。总之，这些发现揭示了Rap 2B作为乳腺癌治疗靶点的可能性。
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.