Our analysis reveals underappreciated levels of diversity and conservation in PPAR genes that could lay the groundwork for therapeutic strategies targeting tumor metabolism, immunity, and hypoxia.
PFCAs, especially those having longer carbon chain lengths (≥C6), are associated with developmental and hormonal effects, immunotoxicity, and promote tumor growth in rodents through their role as PPARα agonists.
5) Peroxisome proliferators do not promote tumour formation in human liver as opposed to mouse liver because of structural and functional differences between human and mouse PPARα.
Activation of peroxisome proliferator-activated receptor α (PPARα) has been demonstrated to inhibit tumor growth and angiogenesis, yet the mechanisms behind these actions remain to be characterized.
PPARα was previously indicated by us as a potential therapeutic target for this neoplasm, due to the malignancy grade dependency of its expression, being particularly abundant in GB.
PPARα is a nuclear receptor protein that functions as a transcription factor for genes including those encoding enzymes involved in energy metabolism; while PPARα has been reported to regulate tumor growth in several cancers, it has not been evaluated in RCC.
Our findings may also reveal the possibility of using the level of endogenous PPARγ ligands and the activities of PPARγ or PPARα as tumor markers for lung cancer.
Multivariate Cox analyses indicated that tumor size (<i>P</i>=0.001), TNM stage (<i>P</i><0.001), vascular invasion (<i>P</i><0.001), and PPARα expression in the cytoplasm (<i>P</i><0.001) were found to be independent prognostic variables for overall survival.
ANGPTL4, originally identified as a peroxisome proliferator-activated receptor alpha and gamma target gene, has potential for use as a new diagnostic tool and a potential therapeutic target, modulating angiogenesis both in tumors and in ischemic tissues.
These data suggest that the decreased drug sensitivity of PPAR gamma1(tr)-expressing cells may be associated with increased tumor aggressiveness and poor clinical prognosis of patients.
In the present study, we show that tumour promoter PMA-mediated induction of genes that are significantly associated with inflammation, tumour growth and metastasis, such as COX-2 (cyclo-oxygenase 2) and VEGF (vascular endothelial growth factor), is inhibited by PPARalpha ligands in the human colorectal carcinoma cell line SW620.
Activation of peroxisome proliferator-activated receptor alpha (PPARα) has been reported to disrupt tumour metabolism and to promote anticancer activity through interfering with the Warburg effect.
To study the role of the PPARalpha receptor and of its Cyp2c epoxygenase gene target in tumorigenesis, we treated mice injected with tumor cells with Wy-14,643, a PPARalpha-selective ligand.
Based on these studies, it was demonstrated that the liver tumors were mediated by a mode of action (MoA) involving nuclear receptors (NRs) through the following key events: (1) CAR and PPAR-α receptor activation, (2) increased hepatocellular proliferation, eventually leading to (3) hepatocellular tumors.
Here, we show that PPARalpha controls SMC cell-cycle progression at the G1/S transition by targeting the cyclin-dependent kinase inhibitor and tumor suppressor p16(INK4a) (p16), resulting in an inhibition of retinoblastoma protein phosphorylation.
Upstream regulator analysis highlighted transcriptional regulation by peroxisome proliferator-activated receptor alpha (PPARα) in the liver and kidney and by tumor protein/suppressor p53 (TP53) in the thymus, spleen, and liver.
Whereas, after the addition of circPVT1, this effect no longer worked, suggesting that circPVT1 may affect the malignancy of the tumor by affecting miRNA and regulating the levels of Paxs and PPARs.