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The aryl hydrocarbon receptor (AhR) is a transcription factor localized in a cytosolic complex with c\u2010Src, which allows it to trigger nongenomic effects through c\u2010Src. Considering that the slightly acidic tumor microenvironment promotes breast cancer progression in a similar way to the AhR\/c\u2010Src axis, our aim was to evaluate whether this pathway could be activated by low pHe. We examined the effect of pHe 6.5 on AhR\/c\u2010Src axis using two breast cancer cell lines (MDA\u2010MB\u2010231 and LM3) and mammary epithelial cells (NMuMG) and found that acidosis increased c\u2010Src phosphorylation only in tumor cells. Moreover, the presence of AhR inhibitors prevented c\u2010Src activation. Low pHe reduced intracellular pH (pHi), while amiloride treatment, which is known to reduce pHi, induced c\u2010Src phosphorylation through AhR. Analyses were conducted on cell migration and metalloproteases (MMP)\u20102 and \u20109 activities, with results showing an acidosis\u2010induced increase in MDA\u2010MB\u2010231 and LM3 cell migration and MMP\u20109 activity, but no changes in NMuMG cells. Moreover, all these effects were blocked by AhR and c\u2010Src inhibitors. In conclusion, acidosis stimulates the AhR\/c\u2010Src axis only in breast cancer cells, increasing cell migration and MMP\u20109 activity. Although the AhR activation mechanism still remains elusive, a reduction in pHi may be thought to be involved. These findings suggest a critical role for the AhR\/c\u2010Src axis in breast tumor progression stimulated by an acidic microenvironment.<\/jats:p>","DOI":"10.1002\/jcb.30275","type":"journal-article","created":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T06:03:40Z","timestamp":1652249020000},"page":"1197-1206","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Extracellular acidosis stimulates breast cancer cell motility through aryl hydrocarbon receptor and c\u2010src kinase activation"],"prefix":"10.1002","volume":"123","author":[{"given":"Noelia V.","family":"Miret","sequence":"first","affiliation":[{"name":"Laboratorio de Efectos Biol\u00f3gicos de Contaminantes Ambientales, Departamento de Bioqu\u00edmica Humana, Facultad de Medicina Universidad de Buenos Aires  Paraguay 2155, 5\u00b0 piso, (CP 1121) Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena V.","family":"Z\u00e1rate","sequence":"additional","affiliation":[{"name":"Laboratorio de Efectos Biol\u00f3gicos de Contaminantes Ambientales, Departamento de Bioqu\u00edmica Humana, Facultad de Medicina Universidad de Buenos Aires  Paraguay 2155, 5\u00b0 piso, (CP 1121) Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Erra D\u00edaz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y SIDA (CONICET), Facultad de Medicina Universidad de Buenos Aires  Paraguay 2155, 11\u00b0 piso, (CP 1121) Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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