# Rap2B promotes proliferation, migration, and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway

## TL;DR

Rap2B promotes breast cancer growth and spread by activating a calcium-related signaling pathway involving ERK1/2.

## Contribution

This study identifies Rap2B as a novel driver of breast cancer progression via calcium-regulated ERK1/2 signaling.

## Key findings

- Rap2B expression is higher in breast cancer cells compared to normal breast cells.
- Rap2B increases intracellular calcium levels and ERK1/2 phosphorylation, promoting cancer cell proliferation and migration.
- Inhibiting calcium or ERK1/2 signaling reverses Rap2B's effects on cancer progression.

## 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.