RANKL-induced migration of MDA-MB-231 human breast cancer cells via Src and MAPK activation

  • Authors:
    • Zhen-Ning Tang
    • Fan Zhang
    • Peng Tang
    • Xiao-Wei Qi
    • Jun Jiang
  • View Affiliations

  • Published online on: June 30, 2011     https://doi.org/10.3892/or.2011.1368
  • Pages: 1243-1250
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Abstract

Accumulating studies have shown that the receptor activator of nuclear factor-κB ligand (RANKL)/RANK pathway plays an important role in tumor metastasis. However, the involvement of the RANKL/RANK signal transduction pathway in breast cancer metastasis remains unclear. The present study, therefore, investigated the role of downstream molecules of RANKL/RANK signaling in breast cancer cells using Transwell chemotaxis assays. RANKL was shown to direct the migration of MDA-MB-231 breast cancer cells. Osteoprotegerin (OPG; soluble decoy receptor of RANKL) inhibited RANKL-induced migration. RANKL activated Src kinase in MDA-MB-231 cells, as shown by Western blotting, and pretreatment with a Src inhibitor abrogated RANKL-induced cell migration, in a similar manner to OPG. Short-hairpin RNA against RANK, delivered via a lentiviral vector, significantly abolished the expression of phosphorylated Src. Stimulation by RANKL induced the phosphorylation of mitogen-activated protein kinases (MAPKs) (ERK, p38, JNK), and specific inhibitors of MAPKs blocked RANKL-induced cell migration. Furthermore, the expression of phosphorylated MAPKs could be blocked by a Src inhibitor and by small interfering RNA against Src. These findings suggest that Src and MAPK pathways may be involved in RANKL-induced MDA-MB-231 breast cancer cell migration.

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November 2011
Volume 26 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Tang Z, Zhang F, Tang P, Qi X and Jiang J: RANKL-induced migration of MDA-MB-231 human breast cancer cells via Src and MAPK activation. Oncol Rep 26: 1243-1250, 2011.
APA
Tang , Z., Zhang, F., Tang, P., Qi, X., & Jiang, J. (2011). RANKL-induced migration of MDA-MB-231 human breast cancer cells via Src and MAPK activation. Oncology Reports, 26, 1243-1250. https://doi.org/10.3892/or.2011.1368
MLA
Tang , Z., Zhang, F., Tang, P., Qi, X., Jiang, J."RANKL-induced migration of MDA-MB-231 human breast cancer cells via Src and MAPK activation". Oncology Reports 26.5 (2011): 1243-1250.
Chicago
Tang , Z., Zhang, F., Tang, P., Qi, X., Jiang, J."RANKL-induced migration of MDA-MB-231 human breast cancer cells via Src and MAPK activation". Oncology Reports 26, no. 5 (2011): 1243-1250. https://doi.org/10.3892/or.2011.1368