Serna-Marquez Nathalia, Diaz-Aragon Ricardo, Reyes-Uribe Emmanuel, Cortes-Reynosa Pedro, Salazar Eduardo Perez
Departamento de Biologia Celular, Cinvestav-IPN, Av IPN # 2508, San Pedro Zacatenco, 07360, Ciudad de Mexico, Mexico.
Med Oncol. 2017 Jun;34(6):111. doi: 10.1007/s12032-017-0969-3. Epub 2017 Apr 29.
An increased risk of developing breast cancer has been associated with high levels of dietary fat intake. Linoleic acid (LA) is an essential fatty acid and the major ω-6 polyunsaturated fatty acid in occidental diets, which is able to induce inappropriate inflammatory responses that contribute to several chronic diseases including cancer. In breast cancer cells, LA induces migration. However, the signal transduction pathways that mediate migration and whether LA induces invasion in MDA-MB-231 breast cancer cells have not been studied in detail. We demonstrate here that LA induces Akt2 activation, invasion, an increase in NFκB-DNA binding activity, miR34a upregulation and miR9 downregulation in MDA-MB-231 cells. Moreover, Akt2 activation requires EGFR and PI3K activity, whereas migration and invasion are dependent on FFAR4, EGFR and PI3K/Akt activity. Our findings demonstrate, for the first time, that LA induces migration and invasion through an EGFR-/PI3K-/Akt-dependent pathway in MDA-MB-231 breast cancer cells.
乳腺癌发病风险的增加与饮食中高脂肪摄入有关。亚油酸（LA）是一种必需脂肪酸，也是西方饮食中主要的ω-6多不饱和脂肪酸，它能够引发不适当的炎症反应，进而导致包括癌症在内的多种慢性疾病。在乳腺癌细胞中，LA可诱导细胞迁移。然而，介导迁移的信号转导途径以及LA是否能诱导MDA-MB-231乳腺癌细胞侵袭尚未得到详细研究。我们在此证明，LA可诱导MDA-MB-231细胞中Akt2激活、侵袭、NFκB-DNA结合活性增加、miR34a上调和miR9下调。此外，Akt2激活需要EGFR和PI3K活性，而迁移和侵袭则依赖于FFAR4、EGFR和PI3K/Akt活性。我们的研究结果首次表明，LA通过EGFR-/PI3K-/Akt依赖途径诱导MDA-MB-231乳腺癌细胞迁移和侵袭。
