Biology of PPAR gamma in cancer: a critical review on existing lacunae

Abstract

Peroxisomal proliferator activated receptor gamma (PPARgamma) belongs to the family of nuclear hormone receptors (NHRs), which directly regulate transcription of target genes. The regulatory role of this receptor on lipid metabolism and insulin sensitization is well established. Recently, the overexpression of this receptor in many human cancers has been identified and understanding its biological significance forms the current theme. PPARgamma activation by specific agonists leads to growth inhibition, apoptosis and differentiation of tumor cells. PPARgamma possess evident tumor promoting properties but the receptor independent effects of its ligands compound the understanding of its biology in cancers. This review highlights the multifaceted role of PPARgamma in cancer progression with specific reference to colon, breast, gastric, lung and urological cancers. Molecular events as well as the mediators involved are analyzed in detail along with PPARgamma independent effects of ligands under each cancer type. The crucial cross talk that exists between Wnt and PPARgamma signaling is also summarized. An attempt has been made to identify the existing lacunae in understanding the biology of PPARgamma in cancers along with suggestions for possible rectification.