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Published on: October 27, 2014
WWOX, the tumour suppressor gene affected in multiple cancers
U Lewandowska1, M Zelazowski, K Seta
1Department of Medical Enzymology, Medical University of Lodz, Poland.
Summary
The WW domain-containing oxidoreductase (WWOX) gene acts as a tumor suppressor, with its loss linked to aggressive cancers. Despite rare biallelic inactivation, reduced WWOX expression correlates with poor prognosis in various cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The WW domain-containing oxidoreductase (WWOX) gene is a known tumor suppressor.
- WWOX is frequently affected in breast, prostate, and ovarian cancers.
- It is located at the chromosomal fragile site FRA16D (16q23.3-24.1).
Purpose of the Study:
- To investigate the role of WWOX in tumorigenesis and cancer prognosis.
- To understand the mechanisms of WWOX tumor suppressor activity.
- To correlate WWOX expression levels with clinical outcomes in various cancers.
Main Methods:
- Analysis of WWOX gene status (allelic inactivation) in cancer cell lines.
- Correlation studies between WWOX expression and tumor aggressiveness/prognosis.
- Functional assays assessing the impact of ectopic WWOX expression on cancer cell behavior (migration, growth).
Main Results:
- Biallelic inactivation of WWOX is a rare event, unlike classical tumor suppressor genes.
- Loss of WWOX expression is frequently correlated with more aggressive disease and worse prognosis in multiple cancers (breast, lung, bladder, gastric, meningiomas).
- Ectopic WWOX expression promotes cell migration but suppresses anchorage-independent growth and induces normal-like colony formation.
Conclusions:
- WWOX functions as a tumor suppressor through mechanisms beyond classical biallelic inactivation.
- Reduced WWOX expression is a significant biomarker for poor prognosis in various malignancies.
- WWOX plays a complex role in cancer, influencing both cell migration and growth regulation.
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