Role of phospholipase D in migration and invasion induced by linoleic acid in breast cancer cells

Mol Cell Biochem. 2019 Jul;457(1-2):119-132. doi: 10.1007/s11010-019-03517-8. Epub 2019 Mar 15.


Linoleic acid (LA) is an essential and omega-6 polyunsaturated fatty acid that mediates a variety of biological processes, including migration and invasion in breast cancer cells. Phospholipase D (PLD) catalyses the hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline. Increases of expression and activity of PLD are reported in several human cancers, including gastric, colorectal, renal, stomach, lung and breast. In this article, we demonstrate that LA induces an increase of PLD activity in MDA-MB-231 breast cancer cells. Particularly, PLD1 and/or PLD2 mediate migration and invasion induced by LA. Moreover, LA induces increases in number and size of spheroids via PLD activity. FFAR1 also mediates migration and invasion, whereas PLD activation induced by LA requires the activities of FFAR1, FFAR4 and EGFR in MDA-MB-231 cells. In summary, PLD plays a pivotal role in migration and invasion induced by LA in MDA-MB-231 breast cancer cells.

Keywords: Breast cancer; FFAR1; FFAR4; Invasion; Linoleic acid; Migration; PLD; Spheroids.

MeSH terms

  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / pathology
  • Cell Movement / drug effects*
  • Female
  • Humans
  • Linoleic Acid / pharmacology*
  • MCF-7 Cells
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism*
  • Phospholipase D / metabolism*


  • Neoplasm Proteins
  • Linoleic Acid
  • Phospholipase D