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REVIEW ARTICLE

WD repeat domain 4 in tumorigenesis: Molecular mechanisms, cancer-type specific roles, and therapeutic potential

Xun Zou1 ,  Ling Tao2 ,  Bin Liu1*
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1 Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, Jiangsu, China
2 Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Zhongshan Hospital, Fudan University, Shanghai, China
Tumor Discovery, 5830 https://doi.org/10.36922/td.5830
Submitted: 9 November 2024 | Revised: 31 December 2024 | Accepted: 21 January 2025 | Published: 5 February 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

WD repeat domain 4 (WDR4) is an essential member of the WD-repeat protein family, known for its regulatory roles in cellular processes critical to cancer development, including RNA modification, protein stability, cell cycle progression, and apoptosis. Studies have shown that WDR4 plays a pivotal role in tumorigenesis across various cancer types, with a particular focus on breast cancer in this study, where its overexpression is closely associated with aggressive tumor characteristics and poorer patient outcomes. As a scaffold protein, WDR4 is involved in N7-methylguanosine tRNA methylation and ubiquitin-mediated protein degradation, thereby regulating RNA stability, protein synthesis, and cell survival. This review provides a comprehensive analysis of WDR4’s molecular mechanisms, its oncogenic functions across different cancer types, and its interactions with other key factors in the tumor microenvironment, further exploring its potential role in tumor progression. As research on WDR4 progresses, we not only gain a deeper understanding of its complex role in tumor biology but also uncover new therapeutic avenues. In particular, the potential of WDR4 as a biomarker and therapeutic target is increasingly recognized. Despite the challenges faced in its clinical application, such as the difficulty in developing targeted therapies and managing side effects, the future prospects of WDR4 in cancer diagnosis and treatment remain promising, and it is expected to emerge as an effective therapeutic target in the near future.

Keywords
WD repeat domain 4
Tumorigenesis
RNA modification
Tumor microenvironment
Cancer-type specificity
Targeted therapy
Funding
This study was supported by the National Natural Science Foundation of China (82273167, 82304124), Jiangsu Province Basic Research Program Natural Science Foundation (Outstanding Youth Fund Project, BK20220063), the Key Program of Basic Science (Natural Science) of Jiangsu Province (22KJA350001), and the Key Disciplines in the Three-year Plan of Shanghai Municipal Public Health System (2023 – 2025) (GWVI-11.1-42).
Conflict of interest
The authors declare that they have no competing interests.
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Tumor Discovery, Electronic ISSN: 2810-9775 Print ISSN: 3060-8597, Published by AccScience Publishing
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