Role of the V1G1 subunit of V-ATPase in breast cancer cell migration

Abstract V-ATPase is a large multi-subunit complex that regulates acidity of intracellular compartments and of extracellular environment. V-ATPase consists of several subunits that drive specific regulatory mechanisms. The V1G1 subunit, a component of the peripheral stalk of the pump, controls local...

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Autores principales:	Maria De Luca, Roberta Romano, Cecilia Bucci
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3f1512f38ef84c2f9ee9c1fa3fd32bfd
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spelling	oai:doaj.org-article:3f1512f38ef84c2f9ee9c1fa3fd32bfd2021-12-02T11:37:26ZRole of the V1G1 subunit of V-ATPase in breast cancer cell migration10.1038/s41598-021-84222-92045-2322https://doaj.org/article/3f1512f38ef84c2f9ee9c1fa3fd32bfd2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84222-9https://doaj.org/toc/2045-2322Abstract V-ATPase is a large multi-subunit complex that regulates acidity of intracellular compartments and of extracellular environment. V-ATPase consists of several subunits that drive specific regulatory mechanisms. The V1G1 subunit, a component of the peripheral stalk of the pump, controls localization and activation of the pump on late endosomes and lysosomes by interacting with RILP and RAB7. Deregulation of some subunits of the pump has been related to tumor invasion and metastasis formation in breast cancer. We observed a decrease of V1G1 and RAB7 in highly invasive breast cancer cells, suggesting a key role of these proteins in controlling cancer progression. Moreover, in MDA-MB-231 cells, modulation of V1G1 affected cell migration and matrix metalloproteinase activation in vitro, processes important for tumor formation and dissemination. In these cells, characterized by high expression of EGFR, we demonstrated that V1G1 modulates EGFR stability and the EGFR downstream signaling pathways that control several factors required for cell motility, among which RAC1 and cofilin. In addition, we showed a key role of V1G1 in the biogenesis of endosomes and lysosomes. Altogether, our data describe a new molecular mechanism, controlled by V1G1, required for cell motility and that promotes breast cancer tumorigenesis.Maria De LucaRoberta RomanoCecilia BucciNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria De Luca Roberta Romano Cecilia Bucci Role of the V1G1 subunit of V-ATPase in breast cancer cell migration
description	Abstract V-ATPase is a large multi-subunit complex that regulates acidity of intracellular compartments and of extracellular environment. V-ATPase consists of several subunits that drive specific regulatory mechanisms. The V1G1 subunit, a component of the peripheral stalk of the pump, controls localization and activation of the pump on late endosomes and lysosomes by interacting with RILP and RAB7. Deregulation of some subunits of the pump has been related to tumor invasion and metastasis formation in breast cancer. We observed a decrease of V1G1 and RAB7 in highly invasive breast cancer cells, suggesting a key role of these proteins in controlling cancer progression. Moreover, in MDA-MB-231 cells, modulation of V1G1 affected cell migration and matrix metalloproteinase activation in vitro, processes important for tumor formation and dissemination. In these cells, characterized by high expression of EGFR, we demonstrated that V1G1 modulates EGFR stability and the EGFR downstream signaling pathways that control several factors required for cell motility, among which RAC1 and cofilin. In addition, we showed a key role of V1G1 in the biogenesis of endosomes and lysosomes. Altogether, our data describe a new molecular mechanism, controlled by V1G1, required for cell motility and that promotes breast cancer tumorigenesis.
format	article
author	Maria De Luca Roberta Romano Cecilia Bucci
author_facet	Maria De Luca Roberta Romano Cecilia Bucci
author_sort	Maria De Luca
title	Role of the V1G1 subunit of V-ATPase in breast cancer cell migration
title_short	Role of the V1G1 subunit of V-ATPase in breast cancer cell migration
title_full	Role of the V1G1 subunit of V-ATPase in breast cancer cell migration
title_fullStr	Role of the V1G1 subunit of V-ATPase in breast cancer cell migration
title_full_unstemmed	Role of the V1G1 subunit of V-ATPase in breast cancer cell migration
title_sort	role of the v1g1 subunit of v-atpase in breast cancer cell migration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3f1512f38ef84c2f9ee9c1fa3fd32bfd
work_keys_str_mv	AT mariadeluca roleofthev1g1subunitofvatpaseinbreastcancercellmigration AT robertaromano roleofthev1g1subunitofvatpaseinbreastcancercellmigration AT ceciliabucci roleofthev1g1subunitofvatpaseinbreastcancercellmigration
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Role of the V1G1 subunit of V-ATPase in breast cancer cell migration

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