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The SRCIN1/p140Cap adaptor protein negatively regulates the aggressiveness of neuroblastoma.
Grasso, Silvia; Cangelosi, Davide; Chapelle, Jennifer; Alzona, Melissa; Centonze, Giorgia; Lamolinara, Alessia; Salemme, Vincenzo; Angelini, Costanza; Morellato, Alessandro; Saglietto, Andrea; Bianchi, Federico Tommaso; Cabodi, Sara; Salaroglio, Iris Chiara; Fusella, Federica; Ognibene, Marzia; Iezzi, Manuela; Pezzolo, Annalisa; Poli, Valeria; Di Cunto, Ferdinando; Eva, Alessandra; Riganti, Chiara; Varesio, Luigi; Turco, Emilia; Defilippi, Paola.
Afiliación
  • Grasso S; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.
  • Cangelosi D; Laboratory of Molecular Biology, Giannina Gaslini Institute, 16147, Genova, Italy.
  • Chapelle J; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.
  • Alzona M; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.
  • Centonze G; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.
  • Lamolinara A; Department of Medicine and Aging Science, Center of Excellence on Aging and Translational Medicine (CeSi-Met), G. D'Annunzio University, Chieti-Pescara, Italy.
  • Salemme V; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.
  • Angelini C; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.
  • Morellato A; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.
  • Saglietto A; Cardiology Division, Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
  • Bianchi FT; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.
  • Cabodi S; Neuroscience Institute Cavalieri Ottolenghi, Regione Gonzole 10, 10043, Orbassano (TO), Italy.
  • Salaroglio IC; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.
  • Fusella F; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.
  • Ognibene M; Department of Oncology, University of Torino, 10126, Torino, Italy.
  • Iezzi M; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.
  • Pezzolo A; Laboratorio Cellule Staminali Post Natali e Terapie Cellulari, Istituto Giannina Gaslini, Genova, Italy.
  • Poli V; Department of Medicine and Aging Science, Center of Excellence on Aging and Translational Medicine (CeSi-Met), G. D'Annunzio University, Chieti-Pescara, Italy.
  • Di Cunto F; Laboratorio Cellule Staminali Post Natali e Terapie Cellulari, Istituto Giannina Gaslini, Genova, Italy.
  • Eva A; Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126, Torino, Italy.
  • Riganti C; Neuroscience Institute Cavalieri Ottolenghi, Regione Gonzole 10, 10043, Orbassano (TO), Italy.
  • Varesio L; Laboratory of Molecular Biology, Giannina Gaslini Institute, 16147, Genova, Italy.
  • Turco E; Department of Oncology, University of Torino, 10126, Torino, Italy.
  • Defilippi P; Laboratory of Molecular Biology, Giannina Gaslini Institute, 16147, Genova, Italy.
Cell Death Differ ; 27(2): 790-807, 2020 02.
Article en En | MEDLINE | ID: mdl-31285546
Neuroblastoma is the most common extra-cranial pediatric solid tumor, responsible for 13-15% of pediatric cancer death. Its intrinsic heterogeneity makes it difficult to target for successful therapy. The adaptor protein p140Cap/SRCIN1 negatively regulates tumor cell features and limits breast cancer progression. This study wish to assess if p140Cap is a key biological determinant of neuroblastoma outcome. RNAseq profiles of a large cohort of neuroblastoma patients show that SRCIN1 mRNA levels are an independent risk factor inversely correlated to disease aggressiveness. In high-risk patients, CGH+SNP microarray analysis of primary neuroblastoma identifies SRCIN1 as frequently altered by hemizygous deletion, copy-neutral loss of heterozygosity, or disruption. Functional experiments show that p140Cap negatively regulates Src and STAT3 signaling, affects anchorage-independent growth and migration, in vivo tumor growth and spontaneous lung metastasis formation. p140Cap also increases sensitivity of neuroblastoma cells to doxorubicin and etoposide treatment, as well as to a combined treatment with chemotherapy drugs and Src inhibitors. Our functional findings point to a causal role of p140Cap in curbing the aggressiveness of neuroblastoma, due to its ability to impinge on specific molecular pathways, and to sensitize cells to therapeutic treatment. This study provides the first evidence that the SRCIN1/p140Cap adaptor protein is a key player in neuroblastoma as a new independent prognostic marker for patient outcome and treatment. Altogether, these data highlight the potential clinical impact of SRCIN1/p140Cap expression in neuroblastoma tumors, in terms of reducing cytotoxic effects of chemotherapy, one of the main issues for pediatric tumor treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Proteínas Adaptadoras del Transporte Vesicular / Neoplasias Pulmonares / Neuroblastoma Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Infant / Male Idioma: En Revista: Cell Death Differ Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Proteínas Adaptadoras del Transporte Vesicular / Neoplasias Pulmonares / Neuroblastoma Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Infant / Male Idioma: En Revista: Cell Death Differ Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido