Expression and inactivation of osteopontin-degrading PHEX enzyme in squamous cell carcinoma

Página do item simplificado
dc.citation.volume77
dc.contributor.authorNeves, Raquel L. [UNIFESP]
dc.contributor.authorChiarantin, Gabrielly M. D. [UNIFESP]
dc.contributor.authorNascimento, Fabio D.
dc.contributor.authorPesquero, Joao B. [UNIFESP]
dc.contributor.authorNader, Helena B. [UNIFESP]
dc.contributor.authorTersariol, Ivarne L. S. [UNIFESP]
dc.contributor.authorMcKee, Marc D.
dc.contributor.authorCarmona, Adriana K. [UNIFESP]
dc.contributor.authorBarros, Nilana M. T. [UNIFESP]
dc.coverageOxford
dc.date.accessioned2020-08-14T13:44:01Z
dc.date.available2020-08-14T13:44:01Z
dc.date.issued2016
dc.description.abstractProteolytic enzymes mediate the activation or inactivation of many physiologic and pathologic processes. The PHEX gene (Phosphate-regulating gene with homologies to endopeptidase on the X chromosome) encodes a metallopeptidase, which is mutated in patients with a prevalent form (1:20,000) of inherited rickets-X-linked hypophosphatemia (XLH). XLH shows growth retardation, hypophosphatemia, osteo-malacia, and defective renal phosphate reabsorption and metabolism of vitamin D. Most PHEX studies have focused on bone, and recently we identified osteopontin (OPN) as the first protein substrate for PHEX, demonstrating in the murine model of XLH (Hyp mice) an increase in OPN that contributes to the osteomalacia. Besides its role in bone mineralization, OPN is expressed in many tissues, and therein has different functions. In tumor biology, OPN is known to be associated with metastasis. Here, we extend our PHEX-OPN studies to investigate PHEX expression in a squamous cell carcinoma (SCC) cell line and its possible involvement in modulating OPN function. Real-time PCR showed PHEX-OPN co-expression in SCC cells, with sequencing of the 22 exons showing no mutation of the PHEX gene. Although recombinant PHEX hydrolyze SCC-OPN fragments, unlike in bone cells, SCC-PHEX protein was not predominantly at the plasma membrane. Enzymatic activity assays, FACs and immunoblotting analyses demonstrated that membrane PHEX is degraded by cysteine proteases and the decreased PHEX activity could contribute to inappropriate OPN regulation. These results highlight for the first time PHEX in tumor biology. (C) 2016 Elsevier Ltd. All rights reserved.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo, Brazil
dc.description.affiliationUniv Anhanguera Sao Paulo, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, Brazil
dc.description.affiliationUniv Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, Sao Paulo, Brazil
dc.description.affiliationMcGill Univ, Fac Dent, Montreal, PQ, Canada
dc.description.affiliationMcGill Univ, Fac Med, Dept Anat & Cell Biol, Montreal, PQ, Canada
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFAPESP (Fundacao de Amparo a Pesquisa do Estado de sao Paulo)
dc.description.sponsorshipCNPq (Conselho Nacional de Desenvolvimento Cientlfico e Tecnologico)
dc.description.sponsorshipIDFAPESP: 2011/504950
dc.description.sponsorshipIDFAPESP: 2012/224801
dc.description.sponsorshipIDCNPq: 478936/2013-3
dc.format.extent155-164
dc.identifierhttp://dx.doi.org/10.1016/j.biocel.2016.05.016
dc.identifier.citationInternational Journal Of Biochemistry & Cell Biology. Oxford, v. 77, p. 155-164, 2016.
dc.identifier.doi10.1016/j.biocel.2016.05.016
dc.identifier.issn1357-2725
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/57484
dc.identifier.wosWOS:000381649800018
dc.language.isoeng
dc.publisherPergamon-Elsevier Science Ltd
dc.relation.ispartofInternational Journal Of Biochemistry & Cell Biology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectPHEXen
dc.subjectXLHen
dc.subjectSquamous cell carcinomaen
dc.subjectOsteopontinen
dc.subjectTumoren
dc.titleExpression and inactivation of osteopontin-degrading PHEX enzyme in squamous cell carcinomaen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
EPM - Artigos