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dc.contributor.authorVillalba, M.
dc.contributor.authorRedin, E.
dc.contributor.authorExposito, F.
dc.contributor.authorPajares, M. J.
dc.contributor.authorSainz, C.
dc.contributor.authorHervas, D.
dc.contributor.authorGuruceaga, E.
dc.contributor.authorDíaz Lagares, Ángel 
dc.contributor.authorCirauqui, C.
dc.contributor.authorRedrado, M.
dc.contributor.authorValencia, K.
dc.contributor.authorde Andrea, C.
dc.contributor.authorJantus-Lewintre, E.
dc.contributor.authorCamps, C.
dc.contributor.authorLópez López, Rafael 
dc.contributor.authorLahoz, A.
dc.contributor.authorMontuenga, L.
dc.contributor.authorPio, R.
dc.contributor.authorSandoval, J.
dc.contributor.authorCalvo, A.
dc.date.accessioned2021-10-15T11:01:15Z
dc.date.available2021-10-15T11:01:15Z
dc.date.issued2019
dc.identifier.issn2045-2322
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pubmed/31659178
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817908/pdf/41598_2019_Article_51066.pdf
dc.identifier.urihttp://hdl.handle.net/20.500.11940/15507
dc.description.abstractFinding novel targets in non-small cell lung cancer (NSCLC) is highly needed and identification of synthetic lethality between two genes is a new approach to target NSCLC. We previously found that TMPRSS4 promotes NSCLC growth and constitutes a prognostic biomarker. Here, through large-scale analyses across 5 public databases we identified consistent co-expression between TMPRSS4 and DDR1. Similar to TMPRSS4, DDR1 promoter was hypomethylated in NSCLC in 3 independent cohorts and hypomethylation was an independent prognostic factor of disease-free survival. Treatment with 5-azacitidine increased DDR1 levels in cell lines, suggesting an epigenetic regulation. Cells lacking TMPRSS4 were highly sensitive to the cytotoxic effect of the DDR1 inhibitor dasatinib. TMPRSS4/DDR1 double knock-down (KD) cells, but not single KD cells suffered a G0/G1 cell cycle arrest with loss of E2F1 and cyclins A and B, increased p21 levels and a larger number of cells in apoptosis. Moreover, double KD cells were highly sensitized to cisplatin, which caused massive apoptosis (~40%). In vivo studies demonstrated tumor regression in double KD-injected mice. In conclusion, we have identified a novel vulnerability in NSCLC resulting from a synthetic lethal interaction between DDR1 and TMPRSS4.
dc.rightsAtribución 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleIdentification of a novel synthetic lethal vulnerability in non-small cell lung cancer by co-targeting TMPRSS4 and DDR1
dc.typeArtigoes
dc.authorsophosLópez López, Rafael
dc.authorsophosDíaz Lagares, Ángel
dc.identifier.doi10.1038/s41598-019-51066-3
dc.identifier.pmid31659178
dc.identifier.sophos31038
dc.issue.number1
dc.journal.titleScientific Reports
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago de Compostela - Complexo Hospitalario Universitario de Santiago de Compostela::Oncoloxía médica
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS)
dc.page.initial15400es
dc.rights.accessRightsopenAccess
dc.subject.keywordCHUS
dc.subject.keywordIDIS
dc.typefidesArtículo Científico (incluye Original, Original breve, Revisión Sistemática y Meta-análisis)
dc.typesophosArtículo Original
dc.volume.number9


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