Artículo
Extracellular acidosis stimulates breast cancer cell motility through aryl hydrocarbon receptor and c-src kinase activation
Miret, Noelia Victoria
; Zárate, Lorena Vanesa
; Erra Diaz, Fernando Alberto
; Leguizamón, M. Agustina; Pontillo, Carolina Andrea
; Chiappini, Florencia Ana
; Ceballos, Leandro Joaquin; Geffner, Jorge Raúl
; Randi, Andrea Silvana
Fecha de publicación:
05/2022
Editorial:
Wiley-liss, div John Wiley & Sons Inc.
Revista:
Journal of Cellular Biochemistry
ISSN:
0730-2312
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
A reduction in extracellular pH (pHe) is a characteristic of most malignant tumors. The aryl hydrocarbon receptor (AhR) is a transcription factor localized in a cytosolic complex with c-Src, which allows it to trigger nongenomic effects through c-Src. Considering that the slightly acidic tumor microenvironment promotes breast cancer progression in a similar way to the AhR/c-Src 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-Src axis using two breast cancer cell lines (MDA-MB-231 and LM3) and mammary epithelial cells (NMuMG) and found that acidosis increased c-Src phosphorylation only in tumor cells. Moreover, the presence of AhR inhibitors prevented c-Src activation. Low pHe reduced intracellular pH (pHi), while amiloride treatment, which is known to reduce pHi, induced c-Src phosphorylation through AhR. Analyses were conducted on cell migration and metalloproteases (MMP)-2 and -9 activities, with results showing an acidosis-induced increase in MDA-MB-231 and LM3 cell migration and MMP-9 activity, but no changes in NMuMG cells. Moreover, all these effects were blocked by AhR and c-Src inhibitors. In conclusion, acidosis stimulates the AhR/c-Src axis only in breast cancer cells, increasing cell migration and MMP-9 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-Src axis in breast tumor progression stimulated by an acidic microenvironment.
Palabras clave:
ARYL HYDROCARBON RECEPTOR
,
BREAST CANCER
,
C-SRC
,
LOW PH
,
METALLOPROTEASE
,
MIGRATION
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Colecciones
Articulos(INBIRS)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS EN RETROVIRUS Y SIDA
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS EN RETROVIRUS Y SIDA
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Miret, Noelia Victoria; Zárate, Lorena Vanesa; Erra Diaz, Fernando Alberto; Leguizamón, M. Agustina; Pontillo, Carolina Andrea; et al.; Extracellular acidosis stimulates breast cancer cell motility through aryl hydrocarbon receptor and c-src kinase activation; Wiley-liss, div John Wiley & Sons Inc.; Journal of Cellular Biochemistry; 123; 7; 5-2022; 1197-1206
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