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Lung Cancer. 2011 May;72(2):154-9. doi: 10.1016/j.lungcan.2011.01.019. Epub 2011 Feb 26.

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

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Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.


Peroxisome proliferator-activated receptors (PPAR)-γ 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-γ have long been in the clinic for the treatment of type II diabetes and have a very low toxicity profile. Activation of PPAR-γ 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-γ 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-γ cross-regulation with other signaling pathways and its relevance to lung cancer therapy will be discussed.

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