Related Experiment Video
Updated: Apr 18, 2026
Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Regulation of cell signaling and apoptosis by tumor suppressor WWOX
Jui-Yen Lo1, Ying-Tsen Chou1, Feng-Jie Lai2
1Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
Abstract:
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.
Insights
The WWOX gene acts as a tumor suppressor, preventing cancer cell death. WWOX deficiency is linked to chemoresistance, suggesting its potential as a therapeutic target for cancer treatment.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- The WW domain-containing oxidoreductase (WWOX) gene functions as a crucial tumor suppressor in humans.
- Loss of WWOX expression is common in various human cancers and is associated with chemoresistance.
- WWOX deficiency impairs apoptotic cell death in response to diverse stress stimuli.
Purpose of the Study:
- To review recent advances in understanding WWOX's molecular mechanisms in regulating cellular functions and stress responses.
- To explore the role of WWOX in cancer development and chemoresistance.
- To evaluate WWOX as a potential prognostic marker and therapeutic target.
Main Methods:
- Literature review of studies on WWOX gene and protein functions.
- Analysis of WWOX's interactions with signaling molecules.
- Examination of WWOX's role in gene transcription, protein stability, and subcellular localization.
Main Results:
- WWOX regulates cell survival, proliferation, differentiation, autophagy, and metabolism.
- WWOX deficiency is linked to chemoresistance in cancers like squamous cell carcinoma, osteosarcoma, and breast cancer.
- WWOX protein physically interacts with numerous signaling molecules.
Conclusions:
- WWOX plays a significant role in cellular stress responses and tumor suppression.
- Activating WWOX with anticancer drugs may overcome chemoresistance and induce cancer cell death.
- WWOX is a promising prognostic marker and a candidate for targeted cancer therapies.
Related Concept Videos
02:23Abnormal Proliferation
02:54Canonical Wnt Signaling Pathway
02:54Canonical Wnt Signaling Pathway
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...