Regulation of cell signaling and apoptosis by tumor suppressor WWOX

Human fragile WWOX gene encodes a tumor suppressor WW domain-containing oxidoreductase (named WWOX, FOR, or WOX1). Functional suppression of WWOX prevents apoptotic cell death induced by a variety of stress stimuli, such as tumor necrosis factor, UV radiation, and chemotherapeutic drug treatment. Lo...

Full description

Saved in:
Bibliographic Details
Published in:Experimental biology and medicine (Maywood, N.J.) N.J.), 2015-03, Vol.240 (3), p.383-391
Main Authors: Lo, Jui-Yen, Chou, Ying-Tsen, Lai, Feng-Jie, Hsu, Li-Jin
Format: Article
Language:English
Subjects:
Apoptosis - physiology
Drug Resistance, Neoplasm - physiology
Humans
Minireviews
Neoplasms - drug therapy
Neoplasms - physiopathology
Oxidoreductases - physiology
Signal Transduction - physiology
Stress, Physiological - physiology
Tumor Suppressor Protein p53 - physiology
Tumor Suppressor Proteins - physiology
WW Domain-Containing Oxidoreductase
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Human fragile WWOX gene encodes a tumor suppressor WW domain-containing oxidoreductase (named WWOX, FOR, or WOX1). Functional suppression of WWOX prevents apoptotic cell death induced by a variety of stress stimuli, such as tumor necrosis factor, UV radiation, and chemotherapeutic drug treatment. Loss of WWOX gene expression due to gene deletions, loss of heterozygosity, chromosomal translocations, or epigenetic silencing is frequently observed in human malignant cancer cells. Acquisition of chemoresistance in squamous cell carcinoma, osteosarcoma, and breast cancer cells is associated with WWOX deficiency. WWOX protein physically interacts with many signaling molecules and exerts its regulatory effects on gene transcription and protein stability and subcellular localization to control cell survival, proliferation, differentiation, autophagy, and metabolism. In this review, we provide an overview of the recent advances in understanding the molecular mechanisms by which WWOX regulates cellular functions and stress responses. A potential scenario is that activation of WWOX by anticancer drugs is needed to overcome chemoresistance and trigger cancer cell death, suggesting that WWOX can be regarded as a prognostic marker and a candidate molecule for targeted cancer therapies.
ISSN:1535-3702
1535-3699
DOI:10.1177/1535370214566747