| First Author | Berger H | Year | 2013 |
| Journal | Cancer Res | Volume | 73 |
| Issue | 12 | Pages | 3578-90 |
| PubMed ID | 23619236 | Mgi Jnum | J:198441 |
| Mgi Id | MGI:5496744 | Doi | 10.1158/0008-5472.CAN-12-4018 |
| Citation | Berger H, et al. (2013) SOCS3 Transactivation by PPARgamma Prevents IL-17-Driven Cancer Growth. Cancer Res 73(12):3578-3590 |
| abstractText | Activation of the transcription factor PPARgamma by the n-3 fatty acid docosahexaenoic acid (DHA) is implicated in controlling proinflammatory cytokine secretion, but the intracellular signaling pathways engaged by PPARgamma are incompletely characterized. Here, we identify the adapter-encoding gene SOCS3 as a critical transcriptional target of PPARgamma. SOCS3 promoter binding and gene transactivation by PPARgamma 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 PPARgamma by DHA. Furthermore, naive 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 PPARgamma-induced SOCS3 expression prevents IL-17-mediated cancer growth. Cancer Res; 73(12); 3578-90. (c)2013 AACR. |
