Biomolecules & Therapeutics

  • 제33권1호
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  • Pages.143-154
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  • 2025
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Taurine Synthesis by 2-Aminoethanethiol Dioxygenase as a Vulnerable Metabolic Alteration in Pancreatic Cancer

  • Hoonsik Nam (Natural Products Research Institute, College of Pharmacy, Seoul National University) ;
  • Woohyung Lee (Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Yun Ji Lee (Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science & Engineering, Inha University) ;
  • Jin-Mo Kim (Natural Products Research Institute, College of Pharmacy, Seoul National University) ;
  • Kyung Hee Jung (Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science & Engineering, Inha University) ;
  • Soon-Sun Hong (Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science & Engineering, Inha University) ;
  • Song Cheol Kim (Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Sunghyouk Park (Natural Products Research Institute, College of Pharmacy, Seoul National University)
  • 투고 : 2024.05.27
  • 심사 : 2024.06.26
  • 발행 : 2025.01.01
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초록

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 ADO-Taurine 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 ADO-Taurine axis may serve as a biomarker for PDAC prognosis and a therapeutic target.

키워드

과제정보

This work was supported by the National Research Foundation (NRF) grant funded by the Korean government (NRF-2021R1A5A2031612 to S-S.H.), a grant (2021IP0020-1 to S.C.K.) from Asan Institute for Life Sciences, Asan Medical Center, and a Inha University Grant (to K.H.J).

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