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Oleic acid promotes MMP-9 secretion and invasion in breast cancer cells

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Abstract

Epidemiological and animal studies suggest an association between dietary fatty acids and an increase risk of developing breast cancer. Obesity, which is characterized by hyperlipidemia and an elevation of circulating free fatty acids (FFAs), is also associated with enhanced cancer risk. In breast cancer cells, the FFA oleic acid (OA) induces migration, proliferation, prolong survival, invasion, an increase in cellular Ca2+ concentration, MEK1/2, ERK1/2, FAK and Src activation. However, the role of OA on MMP-9 secretion and invasion has not been studied in detail. We demonstrate here that stimulation of MDA-MB-231 breast cancer cells with 200 μM OA induces an increase on MMP-9 secretion through a PKC, Src, and EGFR-dependent pathway, as revealed by gelatin zymography assays. Furthermore, microtubule network mediates MMP-9 secretion induced by OA. In contrast, OA does not induce an increase on MMP-9 secretion in MCF10A cells, whereas it does not induce MMP-9 secretion in MCF12A mammary non-tumorigenic epithelial cells. In addition, OA induces invasion through an EGFR, Gi/Go proteins, MMPs, PKC and Src-dependent pathway, but it is not able to promote invasion in non-invasive MCF-7 breast cancer cells. In summary, our findings demonstrate that OA promotes an increase on MMP-9 secretion and invasion through a PKC, Src, and EGFR-dependent pathway in breast cancer cells.

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Acknowledgments

We are grateful to Nora Ruiz for her technical assistance. This work was supported by grants from CONACYT (43370 and 83802). A. S-G is a recipient of a postdoctoral fellowship from ICyTDF. L. C-S, R. M-O and N. N-T were supported by a CONACYT predoctoral training grant.

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  1. Departamento de Biologia Celular, Cinvestav-IPN, Av IPN # 2508, San Pedro Zacatenco, 07360, Mexico, DF, Mexico

    Adriana Soto-Guzman, Napoleon Navarro-Tito, Luis Castro-Sanchez, Raul Martinez-Orozco & Eduardo Perez Salazar

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  1. Adriana Soto-Guzman
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  2. Napoleon Navarro-Tito
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Correspondence to Eduardo Perez Salazar.

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Adriana Soto-Guzman and Napoleon Navarro-Tito contributed equally to this work.

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10585_2010_9340_MOESM1_ESM.tif

Oleic acid induces invasiveness in MDA-MB-231 breast cancer cells MDA-MB-231 cells held in suspension were treated for 2 h in the absence (-) or presence (+) of 12 μM mitomicyn C (Mit.C), as indicated and then cells were plated on the top of matrigel and treated with 200 μM oleic acid for various times, as indicated. Cell invasion was evaluated after incubation. (TIFF 1733 kb)

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Soto-Guzman, A., Navarro-Tito, N., Castro-Sanchez, L. et al. Oleic acid promotes MMP-9 secretion and invasion in breast cancer cells. Clin Exp Metastasis 27, 505–515 (2010). https://doi.org/10.1007/s10585-010-9340-1

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