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- W2004376172 abstract "Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CAPeroxisome proliferator-activated receptor (PPAR) δ is reported to be deeply implicated in the process of colon carcinogenesis. However, the crosstalk between PPARδ in colon cancer cells and a hypoxic tumor microenvironment is not entirely understood. Hypoxia (<1% O2) and deferoxamine (a hypoxia mimetic) induced the expression of tumor-promoting cytokines, IL-8 and VEGF, in colon cancer cells (HCT116). In contrast, the induction of IL-8 and VEGF by hypoxic stress was greatly attenuated in PPARδ-knockout HCT116 cells. Consistently, while HCT116 cells stimulated with hypoxic stress were able to promote the vascular formation of endothelial cells and the migration of macrophages, the capacity of PPARδ-knockout HCT116 cells to induce angiogenesis and macrophage activation was greatly attenuated. Hypoxic stress enhanced DNA binding activity of PPARδ in HCT116 cells showing PPARδ transactivation was stimulated by hypoxic stress. Overexpression of p300 enhanced deferoxamine-induced transcriptional activation of PPARδ whereas siRNA knockdown of p300 decreased deferoxamine-induced PPARδ transactivation. Inhibition of PI3K/Akt pathway by LY294002 or siRNA-Akt resulted in the decrease of PPARδ transactivation induced by hypoxia and deferoxamine in HCT116 cells. Collectively, the results show that PPARδ plays a role in hypoxic stress-induced cytokine expression in colon cancer cells, leading to the promotion of angiogenesis and macrophage activation in the tumor microenvironment. p300 and the PI3K/Akt pathway participate in the regulation of hypoxic stress-mediated PPARδ transactivation in colon cancer cells. Our results suggest that the positive crosstalk between PPARδ in colon cancer cells and hypoxia in tumor microenvironment aggravate and accelerate the progress of tumorigenesis.Citation Format: Joo Young Lee, Eunshil Jeong, Jung Eun Koo, Sang Hyun Yeon. Hypoxic stress enhances tumorigenic potential of PPARδ in colon cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 497. doi:10.1158/1538-7445.AM2014-497" @default.
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- W2004376172 date "2014-09-30" @default.
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- W2004376172 title "Abstract 497: Hypoxic stress enhances tumorigenic potential of PPARδ in colon cancer cells" @default.
- W2004376172 doi "https://doi.org/10.1158/1538-7445.am2014-497" @default.
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