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Blocking the PAH2 domain of Sin3A inhibits tumorigenesis and confers retinoid sensitivity in triple negative breast cancer.
Bansal, Nidhi; Bosch, Almudena; Leibovitch, Boris; Pereira, Lutecia; Cubedo, Elena; Yu, Jianshi; Pierzchalski, Keely; Jones, Jace W; Fishel, Melissa; Kane, Maureen; Zelent, Arthur; Waxman, Samuel; Farias, Eduardo.
Afiliación
  • Bansal N; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Bosch A; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Leibovitch B; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Pereira L; Division of Hemato-Oncology, Department of Medicine, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • Cubedo E; Division of Hemato-Oncology, Department of Medicine, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • Yu J; Department of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Baltimore, MD, USA.
  • Pierzchalski K; Department of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Baltimore, MD, USA.
  • Jones JW; Department of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Baltimore, MD, USA.
  • Fishel M; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Kane M; Department of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Baltimore, MD, USA.
  • Zelent A; Division of Hemato-Oncology, Department of Medicine, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • Waxman S; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Farias E; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Oncotarget ; 7(28): 43689-43702, 2016 Jul 12.
Article en En | MEDLINE | ID: mdl-27286261
Triple negative breast cancer (TNBC) frequently relapses locally, regionally or as systemic metastases. Development of targeted therapy that offers significant survival benefit in TNBC is an unmet clinical need. We have previously reported that blocking interactions between PAH2 domain of chromatin regulator Sin3A and the Sin3 interaction domain (SID) containing proteins by SID decoys result in EMT reversal, and re-expression of genes associated with differentiation. Here we report a novel and therapeutically relevant combinatorial use of SID decoys. SID decoys activate RARα/ß pathways that are enhanced in combination with RARα-selective agonist AM80 to induce morphogenesis and inhibit tumorsphere formation. These findings correlate with inhibition of mammary hyperplasia and a significant increase in tumor-free survival in MMTV-Myc oncomice treated with a small molecule mimetic of SID (C16). Further, in two well-established mouse TNBC models we show that treatment with C16-AM80 combination has marked anti-tumor effects, prevents lung metastases and seeding of tumor cells to bone marrow. This correlated to a remarkable 100% increase in disease-free survival with a possibility of "cure" in mice bearing a TNBC-like tumor. Targeting Sin3A by C16 alone or in combination with AM80 may thus be a promising adjuvant therapy for treating or preventing metastatic TNBC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Represoras / Tetrahidronaftalenos / Benzoatos / Neoplasias de la Mama Triple Negativas / Neoplasias Mamarias Experimentales / Antineoplásicos Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Oncotarget Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Represoras / Tetrahidronaftalenos / Benzoatos / Neoplasias de la Mama Triple Negativas / Neoplasias Mamarias Experimentales / Antineoplásicos Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Oncotarget Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos