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Annexin A2 regulates AKT upon H2O2-dependent signaling activation in cancer cells

2019-04-07Artigo científico Acesso aberto
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datacite.subject.sdg03:Saúde de Qualidade
datacite.subject.sdg09:Indústria, Inovação e Infraestruturas
datacite.subject.sdg04:Educação de Qualidade
dc.contributor.authorCastaldo, Stéphanie Anais
dc.contributor.authorAjime, Tom
dc.contributor.authorSerrão Fernandes, Lina Gisela
dc.contributor.authorAnastácio, Fábio
dc.contributor.authorRosa, Joana Teixeira
dc.contributor.authorGiacomantonio, Carman Anthony
dc.contributor.authorHowarth, Alison
dc.contributor.authorHill, Richard
dc.contributor.authorMadureira, Patricia
dc.date.accessioned2026-03-02T12:45:33Z
dc.date.available2026-03-02T12:45:33Z
dc.date.issued2019-04-07
dc.description.abstractHydrogen peroxide (H2O2) is a main second messenger in oncogenic signaling networks including the Ras and the growth factor receptor pathways. This is achieved predominantly through the oxidation of redox-sensitive cysteine (Cys) residues in proteins resulting in changes to their structure and function. We previously identified annexin A2 (ANXA2) as a redox regulatory protein that plays an important cellular role during oxidative stress and also promoting tumorigenesis. Here we investigated the role of ANXA2 in the regulation of H2O2-dependent signaling that drives tumor progression. We show that depletion of ANXA2 leads to the enhanced activation of AKT following either EGF/EGFR stimulation or oncogenic Ras transformation. The phosphatase and tensin homologue (PTEN) protein negatively regulates the PI3K/AKT pathway. We demonstrate that ANXA2 via its reactive Cys-8 residue, binds to PTEN and that the co-expression of PTEN and ANXA2, but not ANXA2 Cys-8-Ala mutant, inhibits AKT phosphorylation on Ser 473. These results indicate that ANXA2 is important for PTEN regulation within the PI3K/AKT signaling cascade. Furthermore, we also reveal that ANXA2 inversely regulates the expression of the peroxidase, peroxiredoxin 2, in a reactive oxygen species dependent manner.eng
dc.description.sponsorshipIF/00614/2014/CP12340006; UID/BIM/04773/2013CBMR1334. S.A.C.; WELCOMEII/57/UALG/1050/2011; FPAnr2013-0225
dc.identifier.doi10.3390/cancers11040492
dc.identifier.issn2072-6694
dc.identifier.urihttp://hdl.handle.net/10400.1/28296
dc.language.isoeng
dc.peerreviewedyes
dc.publisherMDPI
dc.relationIdentification and characterization of redox regulatory proteins involved in cancer progression
dc.relation.ispartofCancers
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectANXA2
dc.subjectPTEN
dc.subjectPI3K/AKT
dc.subjectPRDX2
dc.subjectH2O2-dependent signaling
dc.titleAnnexin A2 regulates AKT upon H2O2-dependent signaling activation in cancer cellseng
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberIF/00614/2014/CP1234/CT0006
oaire.awardTitleIdentification and characterization of redox regulatory proteins involved in cancer progression
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00614%2F2014%2FCP1234%2FCT0006/PT
oaire.citation.issue4
oaire.citation.startPage492
oaire.citation.titleCancers
oaire.citation.volume11
oaire.fundingStreamInvestigador FCT
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameSerrão Fernandes
person.familyNameHill
person.familyNameMadureira
person.givenNameLina Gisela
person.givenNameRichard
person.givenNamePatricia
person.identifier.ciencia-id9517-5590-381E
person.identifier.ciencia-id6612-9A86-6929
person.identifier.orcid0000-0001-9952-2228
person.identifier.orcid0000-0003-0394-6048
person.identifier.orcid0000-0002-4856-3908
person.identifier.scopus-author-id55266604200
person.identifier.scopus-author-id10340140500
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
relation.isAuthorOfPublicationb553e017-2cfa-488b-ba7f-306432e6ab5a
relation.isAuthorOfPublicatione67f4a4f-aa35-4740-87b0-0cd07a9e1993
relation.isAuthorOfPublicationa40de6a3-d52d-45dd-8620-cb94a22ebc8f
relation.isAuthorOfPublication.latestForDiscoveryb553e017-2cfa-488b-ba7f-306432e6ab5a
relation.isProjectOfPublication0fdc8db0-1836-46ab-8857-73c19cba688c
relation.isProjectOfPublication.latestForDiscovery0fdc8db0-1836-46ab-8857-73c19cba688c

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