<b>Purpose:</b> Functional variants in the <i>peroxisome proliferator-activated receptor gamma</i> (<i>PPARG</i>) and <i>PPARG co-activator 1</i> (<i>PPARGC1</i>) family (e.g., <i>PPARGC1A</i> and <i>PPARGC1B</i>) genes were predicted to confer susceptibility to colorectal cancer (CRC).
PPARG, the gene encoding the gamma isoform of the peroxisome proliferator-activated receptor (PPARgamma), is highly expressed in normal human pancreatic islet cells, is located at 3p25, and has been reported to sustain loss-of-function mutations in human colorectal carcinomas.
Peroxisome proliferator-activated receptor gamma (PPAR(gamma)) ligands inhibit cell growth of colorectal cancer cells in most experimental models, but no significant effect could be observed in patients with colorectal cancer.
PPARgamma inhibitors also reduced CRC cell migration and invasion in assays in vitro and reduced both the number and size of metastases in a HT-29/SCID xenograft metastatic model of CRC.
Although PPARgamma agonists may not by themselves be capable to induce clinical tumor regression, their combination with chemotherapy drugs or other targeted therapies is worth pursuing in the treatment of colorectal carcinoma.
Here, we analyzed a series of chiral phenoxyacetic acid analogues for their ability to inhibit colorectal cancer (CRC) cells growth by binding PPARγ as partial agonists as assessed in transactivation assays of a PPARG-reporter gene.
Here, we found that 15-hydroxy-eicosatetraenoic acid (15S-HETE), an endogenous ligand for PPARgamma, was significantly decreased in the serum of patients with colorectal cancer.
Here, we provide the first evidence that elevated PPARδ expression and/or activation of PPARδ antagonize the ability of PPARγ to induce colorectal carcinoma cell death.
In conclusion, SOX9, β-catenin and PPARγ expression levels are deregulated in the CRC tissue, and in colon cancer cell lines ligand-dependent PPARγ activation unevenly influences SOX9 and β-catenin expression and subcellular localization, suggesting a variable mechanistic role in colon carcinogenesis.
In summary, we identified a panel of proteins correlated with PPARγ expression that could be associated with CRC unveiling new pathways to be investigated for the selection of novel potential prognostic/predictive biomarkers and/or therapeutic targets.
Influence of tumor peroxisome proliferator-activated receptor gamma and delta expression on postoperative mortality of patients undergoing colorectal cancer surgery.