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SOCS3 transactivation by PPARγ prevents IL-17-driven cancer growth

Berger, Hélène
Végran, Frédérique
Chikh, Madijd
Gilardi, Federica
Ladoire, Sylvain
Bugaut, Hélène
Mignot, Grégoire
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Published in Cancer Research. 2013, vol. 73, no. 12, p. 3578-90
Abstract Activation of the transcription factor PPARγ by the n-3 fatty acid docosahexaenoic acid (DHA) is implicated in controlling proinflammatory cytokine secretion, but the intracellular signaling pathways engaged by PPARγ are incompletely characterized. Here, we identify the adapter-encoding gene SOCS3 as a critical transcriptional target of PPARγ. SOCS3 promoter binding and gene transactivation by PPARγ was associated with a repression in differentiation of proinflammatory T-helper (TH)17 cells. Accordingly, TH17 cells induced in vitro displayed increased SOCS3 expression and diminished capacity to produce interleukin (IL)-17 following activation of PPARγ by DHA. Furthermore, naïve CD4 T cells derived from mice fed a DHA-enriched diet displayed less capability to differentiate into TH17 cells. In two different mouse models of cancer, DHA prevented tumor outgrowth and angiogenesis in an IL-17-dependent manner. Altogether, our results uncover a novel molecular pathway by which PPARγ-induced SOCS3 expression prevents IL-17-mediated cancer growth.
Keywords AnimalsBlotting, WesternCD4-Positive T-Lymphocytes/drug effects/metabolismCell Differentiation/drug effectsCell Line, TumorDietDocosahexaenoic Acids/administration & dosage/pharmacologyFemaleInterleukin-17/metabolismMammary Neoplasms, Experimental/genetics/pathology/prevention & controlMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, NudePPAR gamma/agonists/genetics/metabolismPromoter Regions, Genetic/geneticsRNA InterferenceReverse Transcriptase Polymerase Chain ReactionSuppressor of Cytokine Signaling Proteins/genetics/metabolismTh17 Cells/drug effects/metabolismTranscriptional ActivationTumor Burden/drug effects/genetics
PMID: 23619236
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Research group Groupe Pot-Kreis Caroline (931)
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BERGER, Hélène et al. SOCS3 transactivation by PPARγ prevents IL-17-driven cancer growth. In: Cancer research, 2013, vol. 73, n° 12, p. 3578-90. doi: 10.1158/0008-5472.CAN-12-4018 https://archive-ouverte.unige.ch/unige:33010

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Deposited on : 2014-01-09

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