Free fatty acids enhance breast cancer cell migration through plasminogen activator inhibitor-1 and SMAD4

Chang Hyun Byon, Robert W. Hardy, Changchun Ren, Selvarangan Ponnazhagan, Danny R. Welch, Jay M. McDonald, Yabing Chen

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Obesity is a risk factor for breast cancer and is associated with increased plasma concentrations of free fatty acids (FFAs). We and others have demonstrated that FFA induces plasminogen activator inhibitor-1 (PAI-1) expression in a variety of cells. Emerging evidence supports elevation of PAI-1 as a prognostic marker for breast cancer. Therefore, we hypothesized that FFAs might increase expression of PAI-1 in breast cancer cells and facilitate breast cancer progression. Secreted PAI-1 was higher in invasive and metastatic MDA-MB-231 cells compared with less invasive and non-metastatic Hs578T cells. Utilizing FFAs with different saturation and chain lengths, we demonstrated that linoleic acid induced expression of PAI-1 in MDA-MB-231 cells. Linoleic acid also induced in vitro migration of MDA-MB-231. By contrast, other FFAs tested had little or no effect on PAI-1 expression or migration. Linoleic acid-induced breast cancer cell migration was completely inhibited by virally expressed antisense PAI-1 RNA. Furthermore, increased expression of PAI-1 by FFAs was not detected in the SMAD4-deficient MDA-MB-468 breast carcinoma cells. Electrophoretic mobility-shift assay confirmed that linoleic acid-induced expression of PAI-1 was mediated, at least in part, by SMAD4 in MDA-MB-231 cells. That linoleic acid induces PAI-1 expression in breast cancer cells through SMAD4 provides a novel insight into understanding the relationships between two migration-associated molecules, FFAs, and PAI-1.

Original languageEnglish (US)
Pages (from-to)1221-1228
Number of pages8
JournalLaboratory Investigation
Volume89
Issue number11
DOIs
StatePublished - Nov 2009
Externally publishedYes

Keywords

  • Breast cancer cell
  • Free fatty acids
  • Migration
  • PAI-1
  • SMAD4

ASJC Scopus subject areas

  • General Medicine

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