PPAR Beta/Delta and the Hallmarks of Cancer

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.

Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

“…Recently, intestinal PPARβ/δ was shown to participate in reducing obesity, insulin resistance, and dyslipidemia in mice fed a HFD, but the underlying mechanism is unknown [285]. Notably, outside the scope of this review article, several aspects of PPARβ/δ function are relevant to cancer growth [286].…”

The Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Pan-Cancer

“…Peroxisome proliferator-activated receptor coactivators 1 alpha and beta (PPAGC1A and PPARGC1B, respectively) cooperate with PPARP γ , allowing the subsequent interaction between PPAR γ and other transcription factors [ 31 , 32 ]. Pharmacological activators of PPAR δ also show controversial effects on the hallmarks of caner, which may depend on the type of PPAR δ ligands and target tissues [ 33 , 34 ].…”

PPARs and Angiogenesis—Implications in Pathology

“…PPARγ activation with thiazolidinediones could therefore have deleterious effects in patients with cancer [ 69 ]. In conclusion, PPARβ/δ clearly favors tumor angiogenesis (reviewed in [ 70 ]). Although PPARα and PPARγ have initially been described as anti-angiogenic (reviewed in [ 3 ]), conflicting results have been obtained over the time.…”