Genetic polymorphisms of PPAR genes and human cancers: evidence for gene–environment interactions

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

“…PPARG, encoding PPAR γ , functions as a key regulator of glucose homeostasis and adipocyte differentiation [ 28 ]. Downregulation of PPAR γ is associated with decreased terminal differentiation and cell cycle arrest, which induces cell proliferation and leads to tumorigenesis [ 7 , 29 ]. The potential mechanism was proposed by Drori et al that the PPAR γ -induced differentiation may be mediated by a putative PPAR γ coactivator, HIC5, suggesting the importance of coactivators in PPAR γ signaling [ 30 ].…”

A novel plausible mechanism of NSAIDs-induced apoptosis in cancer cells: the implication of proline oxidase and peroxisome proliferator-activated receptor

“…PPARγ is widely expressed in brown and white adipose tissue, spleen and large intestine [64,65]. PPARγ has three isoforms which are transcribed on the same gene but undergo control of different promoters [66].…”

The Relationship Between the PPARδ-87T>C Polymorphism and Colorectal Cancer Risk in a Chinese Han Population

“…Peroxisome proliterator-activated receptors (PPARs) are nuclear hormone receptor-related transcription factors that are activated in response to different ligands. There are three distinct PPAR isoforms (a, β/δ, and y) with specific ligands, functions, and expression patterns in vivo [16], These PPAR family members have been well-documented to serve as key regulators of major chronic diseases such as obesity, atherosclerosis, and cancer [17][18][19].…”

“…PPARδ (also known as PPAR-β or PPAR-β/δ) is expressed at high levels in the skin, intestinal epithelium, and colonic epithelium [20], wherein it functions as an important regulator of lipid and glucose metabolism, PPARδ is responsive to a diverse array of endogenous and xenobiotic ligands [21], with activation of this transcription factor in response to endogenous fatty acid derivatives being closely linked to chronic inflammatory diseases such as ulcerative colitis (UC), Crohn's disease (CD), and CRC [22][23], The activation of PPARδ can further drive the terminal differentiation of intestinal epithelial cells, osteoblasts, keratinocytes, and oligodendrocytes [24]. Two models have been proposed to explain the role of this transcription factor in the context of oncogenesis [16]. These models posit that PPARδ genes can promote tumorigenesis by preventing terminal differentiation and by enhancing cellular proliferation and survival through the upregulation of factors such as IL-8, VEGFS cyclin DI, and COX-2.…”

“…Evidence over the past 20 years has been inconsistent with respect to the role of PPARδ in colorectal tumorigenesis, with some studies having found it to drive tumor development [16,22,[25][26][27][28] and others having found it to inhibit the process [23,[29][30][31], Peters et al noted that the majority of the conflicting evidence regarding the role of PPARδ in this context is primarily associated with its relative expression in colon cancer [32],and COX-2-derived prostaglandin E2 (PGE2) or VEGF can further activate PI3K/Akt signaling to activate additional PPARδ. Furthermore, PPARδ transcriptional activity can be enhanced by Wnt/β-catenin pathway signaling, whereas APC can ablate such signaling and associated transcription [22].…”