Oleic acid promotes migration on MDA-MB-231 breast cancer cells through an arachidonic acid-dependent pathway

Int J Biochem Cell Biol. 2010 Feb;42(2):306-17. doi: 10.1016/j.biocel.2009.11.010. Epub 2009 Nov 18.

Abstract

An association between dietary fatty, obesity and an increased risk of developing breast cancer has been suggested. In breast cancer cells, free fatty acids (FFAs) mediate biological effects including cell proliferation and ERK1/2 activation. However, the contribution of FFAs to tumor progression and metastasis through the regulation of cell migration has not been studied. We demonstrated here that stimulation on MDA-MB-231 breast cancer cells with oleic acid (OA) promotes an increase in focal adhesion kinase (FAK) phosphorylation, as revealed by site-specific antibodies that recognize the phosphorylation state of FAK at tyrosine-397 (Tyr-397), Tyr-577 and in vitro kinase assays. OA also promotes the migration of MDA-MB-231 cells. Treatment with Gi/Go proteins, phospholipase C (PLC), lipoxygenases (LOXs) and Src inhibitor prevents FAK phosphorylation and cell migration. In summary, our findings delineate a new signal transduction pathway, where OA mediates the production of arachidonic acid (AA), and then AA metabolites mediate FAK phosphorylation and cell migration in MDA-MB-231 breast cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acid / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Enzyme Activation / drug effects
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • Humans
  • Oleic Acid / pharmacology*
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Signal Transduction / drug effects*

Substances

  • Arachidonic Acid
  • Oleic Acid
  • Focal Adhesion Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins pp60(c-src)
  • GTP-Binding Protein alpha Subunits, Gi-Go