NOX proteins and ROS generation: role in invadopodia formation and cancer cell invasion

Abstract NADPH oxidases (NOX) are membrane-bound proteins involved in the localized generation of reactive oxygen species (ROS) at the cellular surface. In cancer, these highly reactive molecules primarily originate in mitochondria and via NOX, playing a crucial role in regulating fundamental cellul...

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Main Authors: Nelson Quilaqueo-Millaqueo, David A. Brown-Brown, Jetzabel A. Vidal-Vidal, Ignacio Niechi
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Biological Research
Subjects:
Online Access:https://doi.org/10.1186/s40659-024-00577-z
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author Nelson Quilaqueo-Millaqueo
David A. Brown-Brown
Jetzabel A. Vidal-Vidal
Ignacio Niechi
author_facet Nelson Quilaqueo-Millaqueo
David A. Brown-Brown
Jetzabel A. Vidal-Vidal
Ignacio Niechi
author_sort Nelson Quilaqueo-Millaqueo
collection DOAJ
description Abstract NADPH oxidases (NOX) are membrane-bound proteins involved in the localized generation of reactive oxygen species (ROS) at the cellular surface. In cancer, these highly reactive molecules primarily originate in mitochondria and via NOX, playing a crucial role in regulating fundamental cellular processes such as cell survival, angiogenesis, migration, invasion, and metastasis. The NOX protein family comprises seven members (NOX1-5 and DUOX1-2), each sharing a catalytic domain and an intracellular dehydrogenase site. NOX-derived ROS promote invadopodia formation, aberrant tyrosine kinase activation, and upregulation of matrix metalloproteinases (MMPs). Specifically, NOX5 modulates adhesion, motility, and proteolytic activation, while NOX1 likely contributes to invadopodia formation and adhesive capacity. NOX2 and NOX4 are implicated in regulating the invasive phenotype, expression of MMPs and EMT markers. DUOX1-2 participate in epithelial-mesenchymal transition (EMT), crucial for invasive phenotype development. Soluble molecules such as TGF-β and EGF modulate NOX protein activation, enhancing cell invasion through localized ROS production. This review focuses on elucidating the specific role of NOX proteins in regulating signaling pathways promoting cancer cell spread, particularly EMT, invadopodia formation and invasive capacity.
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institution OA Journals
issn 0717-6287
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spelling doaj-art-e1eb27a0398845cab39c336b77185c672025-08-20T02:31:41ZengBMCBiological Research0717-62872024-12-0157111010.1186/s40659-024-00577-zNOX proteins and ROS generation: role in invadopodia formation and cancer cell invasionNelson Quilaqueo-Millaqueo0David A. Brown-Brown1Jetzabel A. Vidal-Vidal2Ignacio Niechi3Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de ChileInstituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de ChileInstituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de ChileInstituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de ChileAbstract NADPH oxidases (NOX) are membrane-bound proteins involved in the localized generation of reactive oxygen species (ROS) at the cellular surface. In cancer, these highly reactive molecules primarily originate in mitochondria and via NOX, playing a crucial role in regulating fundamental cellular processes such as cell survival, angiogenesis, migration, invasion, and metastasis. The NOX protein family comprises seven members (NOX1-5 and DUOX1-2), each sharing a catalytic domain and an intracellular dehydrogenase site. NOX-derived ROS promote invadopodia formation, aberrant tyrosine kinase activation, and upregulation of matrix metalloproteinases (MMPs). Specifically, NOX5 modulates adhesion, motility, and proteolytic activation, while NOX1 likely contributes to invadopodia formation and adhesive capacity. NOX2 and NOX4 are implicated in regulating the invasive phenotype, expression of MMPs and EMT markers. DUOX1-2 participate in epithelial-mesenchymal transition (EMT), crucial for invasive phenotype development. Soluble molecules such as TGF-β and EGF modulate NOX protein activation, enhancing cell invasion through localized ROS production. This review focuses on elucidating the specific role of NOX proteins in regulating signaling pathways promoting cancer cell spread, particularly EMT, invadopodia formation and invasive capacity.https://doi.org/10.1186/s40659-024-00577-zNOXROSInvadopodiaCancer cell invasion
spellingShingle Nelson Quilaqueo-Millaqueo
David A. Brown-Brown
Jetzabel A. Vidal-Vidal
Ignacio Niechi
NOX proteins and ROS generation: role in invadopodia formation and cancer cell invasion
Biological Research
NOX
ROS
Invadopodia
Cancer cell invasion
title NOX proteins and ROS generation: role in invadopodia formation and cancer cell invasion
title_full NOX proteins and ROS generation: role in invadopodia formation and cancer cell invasion
title_fullStr NOX proteins and ROS generation: role in invadopodia formation and cancer cell invasion
title_full_unstemmed NOX proteins and ROS generation: role in invadopodia formation and cancer cell invasion
title_short NOX proteins and ROS generation: role in invadopodia formation and cancer cell invasion
title_sort nox proteins and ros generation role in invadopodia formation and cancer cell invasion
topic NOX
ROS
Invadopodia
Cancer cell invasion
url https://doi.org/10.1186/s40659-024-00577-z
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AT jetzabelavidalvidal noxproteinsandrosgenerationroleininvadopodiaformationandcancercellinvasion
AT ignacioniechi noxproteinsandrosgenerationroleininvadopodiaformationandcancercellinvasion