Taurine Synthesis by 2-Aminoethanethiol Dioxygenase as a Vulnerable Metabolic Alteration in Pancreatic Cancer
10.4062/biomolther.2024.086
- Author:
Hoonsik NAM
1
;
Woohyung LEE
;
Yun Ji LEE
;
Jin-Mo KIM
;
Kyung Hee JUNG
;
Soon-Sun HONG
;
Song Cheol KIM
;
Sunghyouk PARK
Author Information
1. Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2025;33(1):143-154
- CountryRepublic of Korea
- Language:English
-
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) exhibits an altered metabolic profile compared to normal pancreatic tissue. However, studies on actual pancreatic tissues are limited. Untargeted metabolomics analysis was conducted on 54 pairs of tumor and matched normal tissues. Taurine levels were validated via immunohistochemistry (IHC) on separate PDAC and normal tissues.Bioinformatics analysis of transcriptomics and proteomics data evaluated genes associated with taurine metabolism. Identified taurine-associated gene was validated through gene modulation. Clinical implications were evaluated using patient data. Metabolomics analysis showed a 2.51-fold increase in taurine in PDAC compared to normal tissues (n=54). IHC confirmed this in independent samples (n=99 PDAC, 19 normal). Bioinformatics identified 2-aminoethanethiol dioxygenase (ADO) as a key gene modulating taurine metabolism. IHC on a tissue microarray (39 PDAC, 10 normal) confirmed elevated ADO in PDAC. The ADOTaurine axis correlated with PDAC recurrence and disease-free survival. ADO knockdown reduced cancer cell proliferation and tumor growth in a mouse xenograft model. The MEK-related signaling pathway is suggested to be modulated by ADO-Taurine metabolism. Our multi-omics investigation revealed elevated taurine synthesis mediated by ADO upregulation in PDAC. The ADOTaurine axis may serve as a biomarker for PDAC prognosis and a therapeutic target.
