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.
含有WW结构域的氧化还原酶（WWOX）基因于2000年被发现并克隆，是一个至关重要的肿瘤抑制基因。该基因在多种人类恶性肿瘤中表达频繁下调，且这种下调与肿瘤进展加速及患者预后不良密切相关。WWOX通过与多种关键信号蛋白的直接物理相互作用发挥其肿瘤抑制作用。然而，目前大部分研究仍处于早期阶段，特别是聚焦于WWOX作为生物标志物以及靶向WWOX疗法的研究。此外，相关临床验证明显不足，导致其临床转化前景存在不确定性。本综述重点阐明WWOX在调控癌细胞关键致癌特性方面的重要作用，详细探讨其对细胞失控增殖、侵袭潜能、转移扩散、促进肿瘤生长的代谢重编程、与免疫反应的相互作用以及维持遗传稳定性的影响。在探讨WWOX在癌症生物学中的多种机制作用之后，本综述进一步讨论了靶向WWOX通路的新兴转化潜力，包括其作为预后生物标志物的应用，以及利用WWOX功能或恢复其功能以开发新型癌症治疗策略的进展。
The Role of WWOX in Cancer Progression: Mechanisms and Therapeutic Potential
肿瘤(癌症)患者之家