C-Src-mediated RANKL-induced breast cancer cell migration by activation of the ERK and Akt pathway

Zhang,Lingyun; Teng,Yuee; Zhang,Ye; Liu,Jing; Xu,Ling; Qu,Jinglei; Hou,Kezuo; Yang,Xianghong; Liu,Yunpeng; Qu,Xiujuan

doi:10.3892/ol.2011.487

C-Src-mediated RANKL-induced breast cancer cell migration by activation of the ERK and Akt pathway

Authors:
- Lingyun Zhang
- Yuee Teng
- Ye Zhang
- Jing Liu
- Ling Xu
- Jinglei Qu
- Kezuo Hou
- Xianghong Yang
- Yunpeng Liu
- Xiujuan Qu
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Affiliations: Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, P.R. China, Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110001, P.R. China
Published online on: November 16, 2011 https://doi.org/10.3892/ol.2011.487
Pages: 395-400

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Abstract

The receptor activator for nuclear factor κB ligand/receptor activator for nuclear factor κB (RANKL/RANK) pathway is critical for RANK-expressing cancer cells to home to bones, and c-Src is critical for cancer progression. The objective of this study was to explore the effect of c-Src in the RANKL/RANK pathway and migration activity in human breast cancer cells. Breast cancer cell lines MCF-7, MDA-MB‑231 and BT-474 were obtained and cultured. Flow cytometry was used to examine RANK expression. The results showed that RANK was expressed in breast cancer cell lines MCF-7, MDA-MB‑231 and BT-474, and soluble RANKL (sRANKL)-triggered migration of breast cancer cells by activating ERK1/2, Akt and c-Src. The sRANKL-induced migration was blocked with RANKL inhibitor osteoprotegerin (OPG), MEK inhibitor PD98059, PI3K inhibitor LY294002 and Src inhibitor PP2. Inhibition of c-Src function with PP2 blocked the activation of Akt and ERK1/2, resulting in the inhibition of RANKL-induced migration. In conclusion, RANKL was found to increase the migration of breast cancer cells by activating the c-Src-Akt and c-Src-ERK signaling pathways.

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