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Updated: Jun 7, 2025

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog
Published on: November 5, 2014
RNF4 mediated degradation of PDHA1 promotes colorectal cancer metabolism and metastasis
Jierong Chen1, Zi-Yue Li2, Guansheng Zheng3,4
1Department of Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, PR China.
Abstract:
This study investigates the role of RNF4-mediated ubiquitination and degradation of PDHA1 in colorectal cancer (CRC) metabolism and metastasis. Integrating (The Cancer Genome Atlas) TCGA and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, proteomic, clinical, and metabolomic analyses were performed, revealing PDHA1 as a prognostic marker in CRC. Immunohistochemical staining confirmed lower PDHA1 expression in metastatic CRC tissues. In vitro experiments demonstrated that PDHA1 overexpression inhibited CRC cell proliferation, migration, and invasion. RNF4 was identified as a key mediator in the ubiquitination degradation of PDHA1, influencing glycolytic pathways in CRC cells. Metabolomic analysis of serum samples from metastatic CRC patients further supported these findings. In vivo experiments, including xenograft and metastasis models, validated that RNF4 knockdown stabilized PDHA1, inhibiting tumor formation and metastasis. This study highlights the critical role of RNF4-mediated PDHA1 ubiquitination in promoting glycolytic metabolism, proliferation, and metastasis in CRC.
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