Articles producció científica> Medicina i Cirurgia

Survivin, a key player in cancer progression, increases in obesity and protects adipose tissue stem cells from apoptosis

  • Datos identificativos

    Identificador: imarina:5131228
    Autores:
    Ejarque MCeperuelo-Mallafre VSerena CPachon GNuñez-Alvarez YTerron-Puig MCalvo ENúñez-Roa COliva-Olivera WTinahones FPeinada MAVendrell JFernandez-Veledo S.
    Resumen:
    Adipose tissue (AT) has a central role in obesity-related metabolic imbalance through the dysregulated production of cytokines and adipokines. In addition to its known risk for cardiovascular disease and diabetes, obesity is also a major risk for cancer. We investigated the impact of obesity for the expression of survivin, an antiapoptotic protein upregulated by adipokines and a diagnostic biomarker of tumor onset and recurrence. In a cross-sectional study of 111 subjects classified by body mass index, circulating levels of survivin and gene expression in subcutaneous AT were significantly higher in obese patients and positively correlated with leptin. Within AT, survivin was primarily detected in human adipocyte-derived stem cells (hASCs), the adipocyte precursors that determine AT expansion. Remarkably, survivin expression was significantly higher in hASCs isolated from obese patients that from lean controls and was increased by proinflammatory M1 macrophage soluble factors including IL-1?. Analysis of survivin expression in hASCs revealed a complex regulation including epigenetic modifications and protein stability. Surprisingly, obese hASCs showed survivin promoter hypermethylation that correlated with a significant decrease in its mRNA levels. Nonetheless, a lower level of mir-203, which inhibits survivin protein translation, and higher protein stability, was found in obese hASCs compared with their lean counterparts. We discovered that survivin levels determine the susceptibility of hASCs to apoptotic stimuli (including leptin and hypoxia). Accordingly, hASCs from an obese setting were protected from apoptosis. Collectively, these data shed new light on the molecular mechanisms governing AT expansion in obesity through promotion of hASCs that are resistant to apop
  • Otros:

    Autor según el artículo: Ejarque M; Ceperuelo-Mallafre V; Serena C; Pachon G; Nuñez-Alvarez Y; Terron-Puig M; Calvo E; Núñez-Roa C; Oliva-Olivera W; Tinahones F; Peinada MA; Vendrell J; Fernandez-Veledo S.
    Departamento: Medicina i Cirurgia Ciències Mèdiques Bàsiques
    Autor/es de la URV: Ceperuelo Mallafré, Maria Victoria / Fernandez Veledo, Sonia / Vendrell Ortega, Juan José
    Palabras clave: Proliferation Pathway Leptin Insulin-resistance Inflammation Dna methylation Cycloheximide Breast-cancer Body-weight Adipocytes
    Resumen: Adipose tissue (AT) has a central role in obesity-related metabolic imbalance through the dysregulated production of cytokines and adipokines. In addition to its known risk for cardiovascular disease and diabetes, obesity is also a major risk for cancer. We investigated the impact of obesity for the expression of survivin, an antiapoptotic protein upregulated by adipokines and a diagnostic biomarker of tumor onset and recurrence. In a cross-sectional study of 111 subjects classified by body mass index, circulating levels of survivin and gene expression in subcutaneous AT were significantly higher in obese patients and positively correlated with leptin. Within AT, survivin was primarily detected in human adipocyte-derived stem cells (hASCs), the adipocyte precursors that determine AT expansion. Remarkably, survivin expression was significantly higher in hASCs isolated from obese patients that from lean controls and was increased by proinflammatory M1 macrophage soluble factors including IL-1?. Analysis of survivin expression in hASCs revealed a complex regulation including epigenetic modifications and protein stability. Surprisingly, obese hASCs showed survivin promoter hypermethylation that correlated with a significant decrease in its mRNA levels. Nonetheless, a lower level of mir-203, which inhibits survivin protein translation, and higher protein stability, was found in obese hASCs compared with their lean counterparts. We discovered that survivin levels determine the susceptibility of hASCs to apoptotic stimuli (including leptin and hypoxia). Accordingly, hASCs from an obese setting were protected from apoptosis. Collectively, these data shed new light on the molecular mechanisms governing AT expansion in obesity through promotion of hASCs that are resistant to apoptosis, and point to survivin as a potential new molecular player in the communication between AT and tumor cells. Thus, inhibition of apoptosis targeting survivin might represent an effective strategy for both obesity and cancer therapy.
    Áreas temáticas: Química Psicología Odontología Medicine (miscellaneous) Medicina iii Medicina ii Medicina i Interdisciplinar Immunology Farmacia Engenharias ii Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Cellular and molecular neuroscience Cell biology Cancer research Biotecnología
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 20414889
    Direcció de correo del autor: victoria.ceperuelo@urv.cat sonia.fernandez@urv.cat juanjose.vendrell@urv.cat
    Identificador del autor: 0000-0002-4460-9761 0000-0003-2906-3788 0000-0002-6994-6115
    Fecha de alta del registro: 2024-09-07
    Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
    Enlace a la fuente original: https://www.nature.com/articles/cddis2017209
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referencia al articulo segun fuente origial: Cell Death & Disease. 8 (5): e2802-
    Referencia de l'ítem segons les normes APA: Ejarque M; Ceperuelo-Mallafre V; Serena C; Pachon G; Nuñez-Alvarez Y; Terron-Puig M; Calvo E; Núñez-Roa C; Oliva-Olivera W; Tinahones F; Peinada MA; V (2017). Survivin, a key player in cancer progression, increases in obesity and protects adipose tissue stem cells from apoptosis. Cell Death & Disease, 8(5), e2802-. DOI: 10.1038/cddis.2017.209
    DOI del artículo: 10.1038/cddis.2017.209
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2017
    Tipo de publicación: Journal Publications
  • Palabras clave:

    Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology,Medicine (Miscellaneous)
    Proliferation
    Pathway
    Leptin
    Insulin-resistance
    Inflammation
    Dna methylation
    Cycloheximide
    Breast-cancer
    Body-weight
    Adipocytes
    Química
    Psicología
    Odontología
    Medicine (miscellaneous)
    Medicina iii
    Medicina ii
    Medicina i
    Interdisciplinar
    Immunology
    Farmacia
    Engenharias ii
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Cellular and molecular neuroscience
    Cell biology
    Cancer research
    Biotecnología
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