HPD is an RNA‐Binding Protein Sustaining Ovarian Cancer Cell Glycolysis, Tumor Growth, and Drug Resistance

HPD is an RNA‐Binding Protein Sustaining Ovarian Cancer Cell Glycolysis, Tumor Growth, and Drug Resistance

Abstract 4‐hydroxyphenylpyruvate dioxygenase (HPD) is an important metabolic enzyme in the tyrosine metabolic pathway and displays aberrant expression and function in cancer. Unexpectedly, it is discovered that HPD functions as an RNA‐binding protein (RBP) to drive ovarian cancer progression. HPD is...

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Main Authors: Fei Xie, Han Zhang, Xintong Dai, Mengxin Tu, Chenxi Yu, Lumeng Liu, Yajuan Guo, Huanran Sun, Qingle Gao, Jiyan Wang, Mingming Sun, Qijun Zhang, Taoyuan Wang, Tao He, Zhen Li, Yanping Li, Tao Wang, Jianguo Zhao, Zhongjie Chen, Chunze Zhang, Shuai Zhang, Changliang Shan
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Advanced Science
Subjects:
4‐hydroxyphenylpyruvate dioxygenase (HPD)
glycolysis
mRNA translation
ovarian cancer
RNA‐binding protein
Online Access:https://doi.org/10.1002/advs.202503999
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Summary:Abstract 4‐hydroxyphenylpyruvate dioxygenase (HPD) is an important metabolic enzyme in the tyrosine metabolic pathway and displays aberrant expression and function in cancer. Unexpectedly, it is discovered that HPD functions as an RNA‐binding protein (RBP) to drive ovarian cancer progression. HPD is shown to bind to the RRACH motif of these target mRNAs through its two dsRNA binding domains (RBDs), resulting in increased global mRNA translation. In particular, HPD binding is demonstrated to mediate translation of glycolytic enzymes triosephosphate isomerase (TPI) and alpha‐enolase (ENO1) mRNAs, which facilitates ovarian cancer glycolysis and tumor growth. Thus, targeting the RBD domain of HPD disrupts its RNA binding ability, leading to blocking glycolysis flux, tumor growth, and enhancing drug response. HPD is a novel RNA‐binding protein, and this moonlighting function highlights the knowledge of HPD in regulating cancer development and drug response beyond only as a metabolic enzyme.
ISSN:2198-3844

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