Linoleic acid induces migration and invasion through TLR4 in breast cancer cells

Abstract

Breast cancer is the most diagnosed cancer and the leading cause of cancer-related deaths among worldwide women. Linoleic acid (LA) is an essential omega-6 polyunsaturated fatty acid and the most common polyunsaturated fatty acid in Western diets. Particularly, overweight and obesity are risk factors for breast cancer development in postmenopausal women. LA stimulates an elevation in PLD activity, as well as promotes migration and invasion in MDA-MB-231 breast cancer cells and an epithelial-to-mesenchymal transition process in MCF10A cells. Toll-like receptors (TLRs) are a group of type I transmembrane receptors that have been linked with cancer progression in various types of tumors, including breast cancer. TLR4 is expressed in immune cells, epithelial cells and breast cancer cells, and an inhibition of TLR4 expression in MDA-MB-231 cells promotes a decrease in their viability, proliferation and the secretion of IL-6 and IL-8. This study demonstrates that LA stimulates migration through TLR4 activity in MDA-MB-231 and MCF-7 breast cancer cells. Moreover, LA promotes FAK activation, focal adhesion assembly, an increase in MMP-9 secretion and invasion through TLR4 activity in MDA-MB-231 cells. Our findings demonstrate a signal transduction pathway in which LA activates FFAR1/FFAR4, which in turn activates TLR4 leading to the regulation of specific cellular processes, such as migration and invasion in breast cancer cells.