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

  • Ricardo Diaz-Aragon
  • Javier Ramirez-Ricardo
  • Pedro Cortes-Reynosa
  • Arturo Simoni-Nieves
  • Luis-Enrique Gomez-Quiroz
  • Eduardo Perez SalazarEmail author


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.


Breast cancer Linoleic acid PLD Migration Invasion Spheroids FFAR1 FFAR4 



R. D.-A. and J. R.-R. are supported by a CONACYT Predoctoral training grant.

Author contributions

R. D.-A., J. R.-R. and A. S.-N. performed research and analysed data; L.-E. G.-Q. analysed data; R. D.-A., P. C.-R., and E. P.S. designed the research and analysed data. R. D.-A. and E. P.S. wrote the paper with inputs from all the authors.


This work was supported by a Grant from CONACYT-Mexico (255429) and CONACYT-FOSISS-Mexico (Salud-2015-1-261637).

Compliance with ethical standards

Conflict of interest

Authors declare that there is not conflict of interest.

Supplementary material

11010_2019_3517_MOESM1_ESM.tif (2.2 mb)
Supplementary Figure 1S LA induces an increase in spheroids number and size in MCF-7 cells. Panel A. MCF-7 cells were stimulated with 90 µM LA for 5 days on low-attachment and spheroid formation was evaluated. Panel B. MCF-7 cells were stimulated with 90 µM LA for 15 days on matrigel and spheroid formation was evaluated. One positive control was included (FBS). Images were acquired and analysed for number and/or size. Graphs represent the mean ± SEM of four independent experiments. Scale bar = 300 µm. Asterisks denote comparisons made to unstimulated cells (Basal). **P<0.01, ***P<0.001, ****P<0.0001 (TIF 2213 KB)


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Departamento de Biologia CelularCinvestav-IPNMexicoMexico
  2. 2.Departamento de Ciencias de la SaludUAM-IztapalapaMexico CityMexico

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