ß1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion.

Extracellular matrix (ECM) degradation is a critical process in tumor cell invasion and requires matrix degrading protrusions called invadopodia. The Na(+)/H(+) exchanger (NHE1) has recently been shown to be fundamental in the regulation of invadopodia actin cytoskeleton dynamics and activity. Howev...

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Autores principales:	Ester Antelmi, Rosa A Cardone, Maria R Greco, Rosa Rubino, Francesca Di Sole, Nicola A Martino, Valeria Casavola, Marialuisa Carcangiu, Loredana Moro, Stephan J Reshkin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c46e7b35457241e68fc1e7d1944a891b
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spelling	oai:doaj.org-article:c46e7b35457241e68fc1e7d1944a891b2021-11-18T08:53:55Zß1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion.1932-620310.1371/journal.pone.0075113https://doaj.org/article/c46e7b35457241e68fc1e7d1944a891b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086451/?tool=EBIhttps://doaj.org/toc/1932-6203Extracellular matrix (ECM) degradation is a critical process in tumor cell invasion and requires matrix degrading protrusions called invadopodia. The Na(+)/H(+) exchanger (NHE1) has recently been shown to be fundamental in the regulation of invadopodia actin cytoskeleton dynamics and activity. However, the structural link between the invadopodia cytoskeleton and NHE1 is still unknown. A candidate could be ezrin, a linker between the NHE1 and the actin cytoskeleton known to play a pivotal role in invasion and metastasis. However, the mechanistic basis for its role remains unknown. Here, we demonstrate that ezrin phosphorylated at T567 is highly overexpressed in the membrane of human breast tumors and positively associated with invasive growth and HER2 overexpression. Further, in the metastatic cell line, MDA-MB-231, p-ezrin was almost exclusively expressed in invadopodia lipid rafts where it co-localized in a functional complex with NHE1, EGFR, ß1-integrin and phosphorylated-NHERF1. Manipulation by mutation of ezrins T567 phosphorylation state and/or PIP2 binding capacity or of NHE1s binding to ezrin or PIP2 demonstrated that p-ezrin expression and binding to PIP2 are required for invadopodia-mediated ECM degradation and invasion and identified NHE1 as the membrane protein that p-ezrin regulates to induce invadopodia formation and activity.Ester AntelmiRosa A CardoneMaria R GrecoRosa RubinoFrancesca Di SoleNicola A MartinoValeria CasavolaMarialuisa CarcangiuLoredana MoroStephan J ReshkinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e75113 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ester Antelmi Rosa A Cardone Maria R Greco Rosa Rubino Francesca Di Sole Nicola A Martino Valeria Casavola Marialuisa Carcangiu Loredana Moro Stephan J Reshkin ß1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion.
description	Extracellular matrix (ECM) degradation is a critical process in tumor cell invasion and requires matrix degrading protrusions called invadopodia. The Na(+)/H(+) exchanger (NHE1) has recently been shown to be fundamental in the regulation of invadopodia actin cytoskeleton dynamics and activity. However, the structural link between the invadopodia cytoskeleton and NHE1 is still unknown. A candidate could be ezrin, a linker between the NHE1 and the actin cytoskeleton known to play a pivotal role in invasion and metastasis. However, the mechanistic basis for its role remains unknown. Here, we demonstrate that ezrin phosphorylated at T567 is highly overexpressed in the membrane of human breast tumors and positively associated with invasive growth and HER2 overexpression. Further, in the metastatic cell line, MDA-MB-231, p-ezrin was almost exclusively expressed in invadopodia lipid rafts where it co-localized in a functional complex with NHE1, EGFR, ß1-integrin and phosphorylated-NHERF1. Manipulation by mutation of ezrins T567 phosphorylation state and/or PIP2 binding capacity or of NHE1s binding to ezrin or PIP2 demonstrated that p-ezrin expression and binding to PIP2 are required for invadopodia-mediated ECM degradation and invasion and identified NHE1 as the membrane protein that p-ezrin regulates to induce invadopodia formation and activity.
format	article
author	Ester Antelmi Rosa A Cardone Maria R Greco Rosa Rubino Francesca Di Sole Nicola A Martino Valeria Casavola Marialuisa Carcangiu Loredana Moro Stephan J Reshkin
author_facet	Ester Antelmi Rosa A Cardone Maria R Greco Rosa Rubino Francesca Di Sole Nicola A Martino Valeria Casavola Marialuisa Carcangiu Loredana Moro Stephan J Reshkin
author_sort	Ester Antelmi
title	ß1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion.
title_short	ß1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion.
title_full	ß1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion.
title_fullStr	ß1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion.
title_full_unstemmed	ß1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion.
title_sort	ß1 integrin binding phosphorylates ezrin at t567 to activate a lipid raft signalsome driving invadopodia activity and invasion.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c46e7b35457241e68fc1e7d1944a891b
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ß1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion.

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