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Tumor Discovery

REVIEW ARTICLE
WD repeat domain 4 in tumorigenesis: Molecular

mechanisms, cancer-type specific roles, and
therapeutic potential

Xun Zou 1 , Ling Tao , and Bin Liu *
1
2
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

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
*Corresponding author:
Bin Liu tRNA methylation and ubiquitin-mediated protein degradation, thereby
(liubin@jou.edu.cn) regulating RNA stability, protein synthesis, and cell survival. This review provides a
comprehensive analysis of WDR4’s molecular mechanisms, its oncogenic functions
Citation: Zou X, Tao L,
Liu B. WD repeat domain 4 across different cancer types, and its interactions with other key factors in the tumor
in tumorigenesis: Molecular microenvironment, further exploring its potential role in tumor progression. As
mechanisms, cancer-type specific research on WDR4 progresses, we not only gain a deeper understanding of its complex
roles, and therapeutic potential.
Tumor Discov. 2025;4(1):37-46. role in tumor biology but also uncover new therapeutic avenues. In particular, the
doi: 10.36922/td.5830 potential of WDR4 as a biomarker and therapeutic target is increasingly recognized.
Received: November 9, 2024 Despite the challenges faced in its clinical application, such as the difficulty in
developing targeted therapies and managing side effects, the future prospects of
1st revised: December 31, 2024
WDR4 in cancer diagnosis and treatment remain promising, and it is expected to
2nd revised: January 16, 2025 emerge as an effective therapeutic target in the near future.
Accepted: January 21, 2025
Published online: February 5, Keywords: WD repeat domain 4; Tumorigenesis; RNA modification; Tumor
2025 microenvironment; Cancer-type specificity; Targeted therapy
Copyright: © 2025 Author(s).
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution 1. Introduction
License, permitting distribution,
and reproduction in any medium, 1.1. Molecular and functional overview of WD repeat domain 4 (WDR4)
provided the original work is
properly cited. WDR4 belongs to the WD-repeat protein family, defined by the presence of WD40 repeat
1
Publisher’s Note: AccScience motifs that enable extensive protein-protein interactions. These WD40 domains form
Publishing remains neutral with a stable beta-propeller structure (Figure 1), providing WDR4 with a large interaction
regard to jurisdictional claims in
published maps and institutional surface that supports its role as a scaffold protein in critical cellular pathways. Located
affiliations. on chromosome 21q22.3, WDR4 encodes a protein consisting of 311 amino acids,

Volume 4 Issue 1 (2025) 37 doi: 10.36922/td.5830