Role of LOXs and COX-2 on FAK activation and cell migration induced by linoleic acid in MDA-MB-231 breast cancer cells

• Published in: Cellular oncology (Dordrecht) 2013-02, Vol.36 (1), p.65-77
• Main Authors: Serna-Marquez, Nathalia, Villegas-Comonfort, Socrates, Galindo-Hernandez, Octavio, Navarro-Tito, Napoleon, Millan, Alejandro, Salazar, Eduardo Perez
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Blotting, Western; Breast Neoplasms - enzymology; Breast Neoplasms - pathology; Cancer Research; Cell Line, Tumor; Cell Movement - drug effects; Cell Movement - physiology; Cyclooxygenase 2 - metabolism; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Enzyme Activation - physiology; Female; Focal Adhesion Protein-Tyrosine Kinases - metabolism; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; Humans; Linoleic Acid - pharmacology; Linoleoyl-CoA Desaturase - metabolism; Lipoxygenases - metabolism; Oncology; Original Paper; Pathology; Proto-Oncogene Proteins pp60(c-src) - metabolism; Signal Transduction - drug effects
• ISSN: 2211-3428; 2211-3436
• DOI: 10.1007/s13402-012-0114-4

Background Epidemiological studies and animal models suggest a link between high levels of dietary fat intake and an increased risk of developing breast cancer. Particularly, free fatty acids (FFAs) are involved in several processes, including proliferation, migration and invasion, in breast cancer cells. Linoleic acid (LA) is a dietary n-6 polyunsaturated fatty acid that is known to induce proliferation and invasion in breast cancer cells. So far, however, the contribution of LA to focal adhesion kinase (FAK) activation and cell migration in breast cancer cells has not been studied. Results Here, we show that LA promotes FAK and Src activation, as well as cell migration, in MDA-MB-231 breast cancer cells. FAK activation and cell migration require Src, Gi/Go, COX-2 and LOXs activities, whereas both are independent of Δ6 desaturase activity. In addition, we show that cell migration requires FAK activity, whereas FAK activation requires Src activity, thus suggesting a reciprocal catalytic activation mechanism of FAK and Src. Conclusions In summary, our findings show that LA induces FAK activation and cell migration in MDA-MB-231 breast cancer cells.