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

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.