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

Peroxisomal proliferator activated receptor gamma (PPAR gamma) 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. PPAR gamma activation by specific agonists leads to growth inhibition, apoptosis and differentiation of tumor cells. PPAR gamma 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 PPAR gamma 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 PPAR gamma independent effects of ligands under each cancer type. The crucial cross talk that exists between Wnt and PPAR gamma signaling is also summarized. An attempt has been made to identify the existing lacunae in understanding the biology of PPAR gamma in cancers along with suggestions for possible rectification.