MAPK pathways regulation by DUSP1 in the development of osteosarcoma: Potential markers and therapeutic targets

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dc.citation.issue6
dc.citation.volume56
dc.contributor.authorSilva Lopes, Luana Joyce [UNIFESP]
dc.contributor.authorTesser-Gamba, Francine [UNIFESP]
dc.contributor.authorPetrilli, Antonio Sergio [UNIFESP]
dc.contributor.authorde Seixas Alves, Maria Teresa [UNIFESP]
dc.contributor.authorGarcia-Filho, Reynaldo Jesus [UNIFESP]
dc.contributor.authorCaminada Toledo, Silvia Regina [UNIFESP]
dc.coverageHoboken
dc.date.accessioned2020-07-13T11:53:01Z
dc.date.available2020-07-13T11:53:01Z
dc.date.issued2017
dc.description.abstractOsteosarcoma (OS) is the most frequent primary bone tumor that affect children and adolescents. This tumor is highly aggressive with high risk of metastasis and the implementation of new drugs has not been successful. The search for biomarkers or new therapeutic targets is urgently needed and can help in advances of OS treatment. MAPKs are major signaling transduction molecules that play an important role in regulating a variety of cellular responses. DUSP1 is a phosphatase that dephosphorylates the MAPKs. Both MAPKs and DUSPs have been implicated as major modulators of critical signaling pathways that are dysregulated in various diseases. In a previous study, we found an increase in MAPK7 gene expression contributed for worst overall survival and treatment response. We analyzed gene expression of MAPK pathways that participate in MAPK7 regulation, and DUSP1 gene using paired 28 pre/post-chemotherapy and 12 metastasis OS samples. To understand the DUSP1 role in the pathogenesis of OS, we assessed the function of DUSP1 in four OS cell lines through a series of cellular assays combined with gene silencing technique. Our findings showed increased MAP2K6, MAP4K3, and DUSP1 gene expression in post-chemotherapy OS samples presenting poor prognosis. We also found that the suppression of DUSP1 gene expression resulted in decreased proliferation, migration, and invasion in OS cells. These results suggest that members of MAPK family may be possible prognostic markers in OS and DUSP1 has a relevant role in the OS pathogenesis and can be an attractive therapeutic target in new strategies of OS treatment.en
dc.description.affiliationUniv Fed Sao Paulo, Pediat Oncol Inst IOP GRAACC UNIFESP, Genet Lab, Dept Pediat, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Clin & Expt Oncol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Pediat, Pediat Oncol Inst IOP GRAACC UNIFESP, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Pathol, Pediat Oncol Inst IOP GRAACC UNIFESP, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Orthoped Surg & Traumatol, Pediat Oncol Inst IOP GRAACC UNIFESP, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Morphol & Genet, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Pediat Oncol Inst IOP GRAACC UNIFESP, Genet Lab, Dept Pediat, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Clin & Expt Oncol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Pediat, Pediat Oncol Inst IOP GRAACC UNIFESP, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Pathol, Pediat Oncol Inst IOP GRAACC UNIFESP, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Orthoped Surg & Traumatol, Pediat Oncol Inst IOP GRAACC UNIFESP, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Morphol & Genet, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo
dc.description.sponsorshipPediatric Oncology Institute-GRAACC/UNIFESP
dc.description.sponsorshipIDFAPESP: 2011/10459-5
dc.format.extent1630-1641
dc.identifierhttp://dx.doi.org/10.1002/mc.22619
dc.identifier.citationMolecular Carcinogenesis. Hoboken, v. 56, n. 6, p. 1630-1641, 2017.
dc.identifier.doi10.1002/mc.22619
dc.identifier.issn0899-1987
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54352
dc.identifier.wosWOS:000403698200009
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofMolecular Carcinogenesis
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectosteosarcomaen
dc.subjectDUSP1en
dc.subjectMAPK signaling pathwaysen
dc.subjecttherapeutic targeten
dc.subjectbiomarkersen
dc.titleMAPK pathways regulation by DUSP1 in the development of osteosarcoma: Potential markers and therapeutic targetsen
dc.typeinfo:eu-repo/semantics/article
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