title: Molecular cross-regulation between PPAR-γ and other signaling pathways: implications for lung cancer therapy.
abstract: 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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. ajayar@umich.edu
authors.forename: Ajaya Kumar
authors.initials: AK
authors.lastname: Reka
authors.forename: Moloy T
authors.initials: MT
authors.lastname: Goswami
authors.forename: Rashmi
authors.initials: R
authors.lastname: Krishnapuram
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Standiford
authors.forename: Venkateshwar G
authors.initials: VG
authors.lastname: Keshamouni
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004358:Drug Therapy / Q000639:trends; D006801:Humans; D007249:Inflammation; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D047495:PPAR gamma / Q000819:agonists*; D020239:Receptor Cross-Talk / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D047495:PPAR gamma