Ang II-AT1R increases cell migration through PI3K/AKT and NF-κB pathways in breast cancer

J Cell Physiol. 2014 Nov;229(11):1855-62. doi: 10.1002/jcp.24639.


Angiotensin II (Ang II), a biologically active peptide of the renin-angiotensin system (RAS), plays an important role in promoting cell migration via Angiotensin II type 1 receptor (AT1R). In this study, we examined the mechanisms by which Ang II affected cell migration in AT1R-positive MDA-MB-231 human breast cancer cells. Ang II increased cell migration and expression of matrix metalloproteinase (MMP)-2,-9 in a dose-dependent manner. Ang II-mediated cell migration was reduced by specific blocking of MMP-2 and MMP-9, as well as with pretreatment with inhibitors of AT1R, phosphatidylinositol 3-kinase (PI3K), Akt, and NF-κB. Similarly, Ang II-mediated expression of MMP-2,-9 was downregulated by pretreatment with inhibitors of AT1R and PI3K. In addition, Ang II treatment significantly induced phosphorylation of PI3K, Akt, and resulted in increased NF-κB activity. These findings suggest that Ang II activates the AT1R/PI3K/Akt pathway, which further activates IKKα/β and NF-κB, resulting in enhanced expression of MMP-2,-9 and migration in human breast cancer cells. Therefore, targeting Ang II/AT1R/PI3K/Akt/NF-κB signaling could be a novel anti-metastatic therapy for breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • NF-kappa B / metabolism*
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptor, Angiotensin, Type 1 / metabolism*
  • Signal Transduction / drug effects
  • Up-Regulation / drug effects


  • NF-kappa B
  • Receptor, Angiotensin, Type 1
  • Angiotensin II
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9