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WWOX, the tumour suppressor gene affected in multiple cancers
U Lewandowska1, M Zelazowski, K Seta
1Department of Medical Enzymology, Medical University of Lodz, Poland.
Abstract:
WWOX is a tumour suppressor gene affected in multiple cancers, especially in breast, prostate and ovary. This gene is located at the chromosomal area 16q23.3-24.1, which was identified as a common chromosomal fragile site FRA16D. WWOX turned out to possess tumour suppressor features despite the fact that the most basic (classical) way of tumour suppressor gene inactivation involves both alleles (e.g. through deletions, point mutations and promoter methylation), which is very rare event in a case of WWOX, occurring only in few cell lines. A large number of papers corroborate the phenomenon of correlation between the loss of WWOX expression and more aggressive/worse prognosis in many different types of tumours, for example breast cancer, nonsmall cell lung cancer, bladder cancer, gastric cancer or sporadic meningiomas. Ectopically increased WWOX expression promotes migration through basal membrane, however suppresses anchorage independent growth and induces normal-like colony formation in matrigel.
Insights
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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