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.
<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).
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.
Together, these results suggest that miR-145 is a novel target of PPARγ, acts as a tumor suppressor in CRC cell lines and is a key regulator of intestinal cell differentiation by directly targeting SOX9, a marker of undifferentiated progenitors in the colonic crypts.
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.
Thus, codeficiency of Cav1 and adenomatous polyposis coli facilitated formation of CRC, and activation of PPARg may offer novel strategies for treatment of CRC.
Since higher levels of miR-130b are found in advanced tumor stages (III-IV), we propose a novel role of the miR-130b-PPARγ axis in fostering the progression toward more invasive CRCs.
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.
This meta-analysis suggests that the Ala allele of the PPARgammaP12A polymorphism might be a protective factor for colorectal cancer, but a risk factor for gastric cancer.
This study shows that PPARgamma agonists up-regulate KLF4 expression in receptor-dependent manner, and KLF4 was identified as a novel transcription factor that controls NAG-1 promoter activity in human and mouse colorectal cancers.
We report a novel PPARG germline mutation in a patient affected by colorectal cancer that replaces serine 289 with cysteine in the mature protein (S289C).