Sangeeta Jaiswal1, Bishnu Joshi1, Jing Chen1, Fa Wang1, Michael K Dame1, Jason R Spence1,2,3, Gina M Newsome1, Erica L Katz1, Yatrik M Shah1,4, Sadeesh K Ramakrishnan4, Gaoming Li1, Miki Lee1, Henry D Appelman5, Rork Kuick6, Thomas D Wang1,2,7. 1. Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. 2. Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA. 3. Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA. 4. Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA. 5. Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA. 6. Department of Biostatistics, and University of Michigan, Ann Arbor, Michigan, USA. 7. Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Abstract
Aim: Sessile serrated adenomas (SSAs) are premalignant lesions driven by the BRAFV600E mutation to give rise to colorectal cancers (CRCs). They are often missed during white light colonoscopy because of their subtle appearance. Previously, a fluorescently labeled 7mer peptide KCCFPAQ was shown to detect SSAs in vivo. We aim to identify the target of this peptide. Results: Peroxiredoxin-1 (Prdx1) was identified as the binding partner of the peptide ligand. In vitro binding assays and immunofluorescence staining of human colon specimens ex vivo supported this result. Prdx1 was overexpressed on the membrane of cells with the BRAFV600E mutation, and this effect was dependent on oxidative stress. RKO cells harboring the BRAFV600E mutation and human SSA specimens showed higher oxidative stress as well as elevated levels of Prdx1 on the cell membrane. Innovation and Conclusion: These results suggest that Prdx1 is overexpressed on the cell surface in the presence of oxidative stress and can serve as an imaging biomarker for in vivo detection of SSAs. Antioxid. Redox Signal. 36, 39-56.
Aim: Sessile serrated adenomas (SSAs) are premalignant lesions driven by the BRAFV600E mutation to give rise to colorectal cancers (CRCs). They are often missed during white light colonoscopy because of their subtle appearance. Previously, a fluorescently labeled 7mer peptide KCCFPAQ was shown to detect SSAs in vivo. We aim to identify the target of this peptide. Results: Peroxiredoxin-1 (Prdx1) was identified as the binding partner of the peptide ligand. In vitro binding assays and immunofluorescence staining of human colon specimens ex vivo supported this result. Prdx1 was overexpressed on the membrane of cells with the BRAFV600E mutation, and this effect was dependent on oxidative stress. RKO cells harboring the BRAFV600E mutation and human SSA specimens showed higher oxidative stress as well as elevated levels of Prdx1 on the cell membrane. Innovation and Conclusion: These results suggest that Prdx1 is overexpressed on the cell surface in the presence of oxidative stress and can serve as an imaging biomarker for in vivo detection of SSAs. Antioxid. Redox Signal. 36, 39-56.
Authors: Dhimankrishna Ghosh; Cory C Funk; Juan Caballero; Nameeta Shah; Katherine Rouleau; John C Earls; Liliana Soroceanu; Greg Foltz; Charles S Cobbs; Nathan D Price; Leroy Hood Journal: Cell Syst Date: 2017-03-29 Impact factor: 10.304
Authors: Harminder Singh; Zoann Nugent; Alain A Demers; Erich V Kliewer; Salaheddin M Mahmud; Charles N Bernstein Journal: Gastroenterology Date: 2010-06-20 Impact factor: 22.682