# The Role of WWOX in Cancer Progression: Mechanisms and Therapeutic Potential

## TL;DR

This paper reviews how the WWOX gene acts as a tumor suppressor and its potential as a cancer biomarker and therapeutic target.

## Contribution

The paper provides a comprehensive overview of WWOX's role in cancer progression and its translational potential as a biomarker and therapeutic target.

## Key findings

- WWOX downregulation is linked to increased tumor aggressiveness and poor prognosis in breast cancer.
- WWOX interacts with key signaling proteins to exert tumor-suppressive effects.
- WWOX influences cancer cell proliferation, metastasis, metabolism, and genetic stability.

## Abstract

WW domain-containing oxidoreductase (WWOX), a tumor suppressor, is downregulated in various tumor tissues. It is correlated with tumorigenesis, progression, treatment resistance, and clinical prognosis. For instance, the downregulation of WWOX expression is associated with increased tumor grade and aggressiveness, along with lower recurrence-free and overall survival rates in patients diagnosed with Basal-like and Triple-Negative Breast Cancer. This review provides a comprehensive overview of the structure, function, and role of WWOX in tumors, emphasizing its critical regulatory effects on cancer. Additionally, it discusses the potential applications and future prospects of WWOX as a tumor biomarker and therapeutic target.

Discovered and cloned in 2000, the WW domain-containing oxidoreductase (WWOX) gene serves as a crucial tumor suppressor gene. Its expression is frequently downregulated in a wide spectrum of human malignancies, and this reduction is strongly correlated with accelerated tumor progression and poor patient prognosis. WWOX exerts its tumor-suppressive effects through direct physical interactions with numerous key signaling proteins. However, much of the current research remains in its early stages, particularly studies focusing on WWOX as a biomarker and WWOX-targeting therapies. Furthermore, there is a notable deficiency in related clinical validation, leading to uncertainties regarding clinical translation. This review specifically focuses on elucidating the significant contributions of WWOX in modulating critical oncogenic traits within cancer cells. We detail its impact on uncontrolled proliferation, invasive potential, metastatic spread, metabolic reprogramming that favors tumor growth, interactions with the immune response, and the maintenance of genetic stability. Following this exploration of WWOX’s diverse mechanistic roles in cancer biology, the review further discusses the emerging translational potential of targeting WWOX pathways, including its application as a prognostic biomarker and the development of strategies that exploit WWOX function or restoration for novel cancer therapeutics.