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| Home > Articles > Published articles > Survivin, a key player in cancer progression, increases in obesity and protects adipose tissue stem cells from apoptosis |
| Home > Articles > Published articles > Survivin, a key player in cancer progression, increases in obesity and protects adipose tissue stem cells from apoptosis |
(Hospital Universitari Joan XXIII de Tarragona) (Hospital Universitari Joan XXIII de Tarragona) (Hospital Universitari Joan XXIII de Tarragona) (Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición) (Hospital Universitari Joan XXIII de Tarragona) (Hospital Universitari Joan XXIII de Tarragona)| Date: | 2017 |
| Abstract: | 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 ATwere 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 fromlean controls and was increased by proinflammatory M1 macrophage soluble factors including IL-1β. 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 mRA levels. Nonetheless, a lower level ofmir-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. |
| Grants: | Ministerio de Economía y Competitividad PI14/00228 Ministerio de Economía y Competitividad SAF2015-6519R Instituto de Salud Carlos III CIBERdem/CD07708/0012 Instituto de Salud Carlos III CP10/00438 Instituto de Salud Carlos III CPII16/00008 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Published in: | Cell Death and Disease, Núm. 8 (2017) , p. 1-12 |
