Molecular cross-regulation between PPAR-γ and other signaling pathways: Implications for lung cancer therapy

Peroxisome proliferator-activated receptors (PPAR)-gamma belongs to the nuclear hormone receptor superfamily of ligand-dependent transcription factors. It is a mediator of adipocyte differentiation, regulates lipid metabolism and macrophage function. The ligands of PPAR-gamma have long been in the clinic for the treatment of type II diabetes and have a very low toxicity profile. Activation of PPAR-gamma was shown to modulate various hallmarks of cancer through its pleiotropic affects on multiple different cell types in the tumor microenvironment. An overwhelming number of preclinical-studies demonstrate the efficacy of PPAR-gamma ligands in the control of tumor progression through their affects on various cellular processes, including cell proliferation, apoptosis, angiogenesis, inflammation and metastasis. A variety of signaling pathways have been implicated as potential mechanisms of action. This review will focus on the molecular basis of these mechanisms; primarily PPAR-gamma cross-regulation with other signaling pathways and its relevance to lung cancer therapy will be discussed. (C) 2011 Elsevier Ireland Ltd. All rights reserved.