Targeting Mitochondrial ROS Production to Reverse the Epithelial-Mesenchymal Transition in Breast Cancer Cells.
Curr Issues Mol Biol
; 44(11): 5277-5293, 2022 Oct 29.
Article
en En
| MEDLINE
| ID: mdl-36354671
Experimental evidence implicates reactive oxygen species (ROS) generation in the hypoxic stabilization of hypoxia-inducible factor (HIF)-1α and in the subsequent expression of promoters of tumor invasiveness and metastatic spread. However, the role played by mitochondrial ROS in hypoxia-induced Epithelial-Mesenchymal Transition (EMT) activation is still unclear. This study was aimed at testing the hypothesis that the inhibition of hypoxia-induced mitochondrial ROS production, mainly at the mitochondrial Complex III UQCRB site, could result in the reversion of EMT, in addition to decreased HIF-1α stabilization. The role of hypoxia-induced ROS increase in HIF-1α stabilization and the ability of antioxidants, some of which directly targeting mitochondrial Complex III, to block ROS production and HIF-1α stabilization and prevent changes in EMT markers were assessed by evaluating ROS, HIF-1α and EMT markers on breast cancer cells, following 48 h treatment with the antioxidants. The specific role of UQCRB in hypoxia-induced EMT was also evaluated by silencing its expression through RNA interference and by assessing the effects of its downregulation on ROS production, HIF-1α levels, and EMT markers. Our results confirm the pivotal role of UQCRB in hypoxic signaling inducing EMT. Thus, UQCRB might be a new therapeutic target for the development of drugs able to reverse EMT by blocking mitochondrial ROS production.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Curr Issues Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2022
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Suiza