Role of WWOX and NF‐κB in lung cancer progression (1049.2)
Abstract
The pro‐inflammatory, pro‐survival transcription factor NF‐κB is considered as 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2014
- Source ID
- 10.1096/fasebj.28.1_supplement.1049.2
Entities
People
- Nan‐shan Chang
Organizations
- National Cheng Kung University
- United States Department of Defense