title: Role of WWOX and NF-κB in lung cancer progression.
abstract: It is generally agreed that the pro-inflammatory, pro-survival transcription factor NF-κB is a tumor promoter. Tumor necrosis factor alpha (TNF-α or TNF) mediates NF-κB activation. Tumor suppressor WWOX (FOR or WOX1) is a downstream effector of the TNF signaling. Thus, activation of both WWOX (FOR or WOX1) and NF-κB may occur during TNF signaling and/or under stress conditions. Indeed, the first WW domain of WWOX induces the activation of NF-κB-responsive promoter without TNF participation. It appears that WWOX counteracts with NF-κB in regulating cell survival and death. For example, WWOX becomes activated with Tyr33 phosphorylation and relocates together with NF-κB and many transcription factors to the nucleus to cause neuronal death in sciatic nerve-transected rats. While WWOX is frequently lost in lung cancer and many other cancers, NF-κB activation-induced cancer promotion probably requires WWOX-independent signaling networks to induce expression of pro-survival factors. The antagonistic role of WWOX and NF-κB in the regulation of lung cancer progression is discussed.
authors.affiliation: Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan.
authors.forename: Szu-Jung
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan.
authors.forename: Shenq-Shyang
authors.initials: SS
authors.lastname: Huang
authors.affiliation: Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan. wox1world@gmail.com.|Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA. wox1world@gmail.com.|Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA. wox1world@gmail.com.
authors.forename: Nan-Shan
authors.initials: NS
authors.lastname: Chang
keywords: Lung cancer; NF-κB; Tumor necrosis factor; Tumor suppressor; WWOX