Acidosis promotes breast cancer cell migration through the AhR / c-Src signaling pathway

MIRET NOELIA; ZARATE LORENA; ERRA DÍAZ, FERNANDO; PONTILLO CAROLINA; CEBALLOS LEANDRO; CHIAPPINI FLORENCIA; GEFFNER, JORGE; RANDI ANDREA

Congreso; Reunión anual de Sociedades Biocientíficas 2019 LXIV Reunión Anual de la SAIC; 2019

A reduction in extracellular pH (pHe) is a characteristic of most malignant tumors. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factorlocalized in a cytosolic complex with c-Src kinase, allowing it to triggernon-genomic effects through c-Src. Considering that the slightly acidic tumor microenvironment promotes breast cancer progression in a similar way to the AhR/c-Srcaxis, we propose that this pathway could be activated by the change in the pHe. We evaluated the effect of pHe 6.5 on AhR/c-Srcaxis (WB) in two breast cancer cell lines (MDA-MB-231 and LM3) and in a mammary epithelial cell line (NMuMG),as well as its correlation with cell migration (wound healing assay) and metalloproteases (MMP)-2 and 9 activities (zymography). The pHe was adjusted with an isotonic solution of HCl.Results showed that acidosisincreasedc-Src phosphorylation only in breast cancer cells (MDA-MB-231 at 4-6 h, p