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Abstract
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family. Three different isoforms, PPAR alpha, PPAR beta/delta and PPAR gamma have been identified. They all form heterodimers with retinoic X receptors to activate or repress downstream target genes dependent on the presence/absence of ligands and coactivators or corepressors. PPARs differ in their tissue expression profile, ligands and specific agonists and antagonists. PPARs attract attention as potential therapeutic targets for a variety of diseases. PPAR alpha and gamma agonists are in clinical use for the treatment of dyslipidemias and diabetes. For both receptors, several clinical trials as potential therapeutic targets for cancer are ongoing. In contrast, PPAR beta/delta has been suggested as a therapeutic target for metabolic syndrome. However, potential risks in the settings of cancer are less clear. A variety of studies have investigated PPAR beta/delta expression or activation/inhibition in different cancer cell models in vitro, but the relevance for cancer growth in vivo is less well documented and controversial. In this review, we summarize critically the knowledge of PPAR beta/delta functions for the different hallmarks of cancer biological capabilities, which interplay to determine cancer growth.
Highlights
Peroxisome proliferator-activated receptors (PPARs) belong to the group of nuclear receptors.They exist in three different isoforms: PPARα (NR1C1), PPARβ/δ (NR1C2) and PPARγ (NR1C3).They heterodimerize with RXR; and upon ligand binding act mainly as transcriptional regulators of specific target genes
We showed in liposarcoma cell lines that PPARβ/δ activation increases proliferation, which is abolished by a PPARβ/δ–siRNA or a specific PPARβ/δ antagonist
We summarized here known PPARβ/δ effects on cell proliferation, induction of angiogenesis, cell death, function of tumor suppressors, replicative immortality and senescence, invasion and metastasis, tumor metabolism and immune function and mentioned underlying molecular mechanisms
Summary
Peroxisome proliferator-activated receptors (PPARs) belong to the group of nuclear receptors They exist in three different isoforms: PPARα (NR1C1), PPARβ/δ (NR1C2) and PPARγ (NR1C3). They heterodimerize with RXR; and upon ligand binding act mainly as transcriptional regulators of specific target genes. The protein expression is globally described, but not annotated to certain cell types in the different tumors. Several aspects of PPARβ/δ function with relevance for cancer growth have been reviewed recently [1,5,6,9,10,11]. For simplification, we will summarize in this chapter the published results on cell proliferation as well as on general tumor growth.
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