en
Scientific article
Open access
English

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

Published inCancer research, vol. 73, no. 12, p. 3578-3590
Publication date2013
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
  • Animals
  • Blotting, Western
  • CD4-Positive T-Lymphocytes/drug effects/metabolism
  • Cell Differentiation/drug effects
  • Cell Line, Tumor
  • Diet
  • Docosahexaenoic Acids/administration & dosage/pharmacology
  • Female
  • Interleukin-17/metabolism
  • Mammary Neoplasms, Experimental/genetics/pathology/prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • PPAR gamma/agonists/genetics/metabolism
  • Promoter Regions, Genetic/genetics
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Suppressor of Cytokine Signaling Proteins/genetics/metabolism
  • Th17 Cells/drug effects/metabolism
  • Transcriptional Activation
  • Tumor Burden/drug effects/genetics
Citation (ISO format)
BERGER, Hélène et al. SOCS3 transactivation by PPARγ prevents IL-17-driven cancer growth. In: Cancer research, 2013, vol. 73, n° 12, p. 3578–3590. doi: 10.1158/0008-5472.CAN-12-4018
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal0008-5472
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