Journal
ANTIOXIDANTS & REDOX SIGNALING
Volume 36, Issue 1-3, Pages 39-56Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2020.8244
Keywords
peroxiredoxin-1; sessile serrated adenoma; oxidative stress; KCC; BRAF
Funding
- National Institutes of Health [R01 CA1933377, U01 EB028235, P30 CA046592, R01 CA148828]
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The study identified 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.
Aim: Sessile serrated adenomas (SSAs) are premalignant lesions driven by the BRAF(V600E) 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 BRAF(V600E) mutation, and this effect was dependent on oxidative stress. RKO cells harboring the BRAF(V600E) 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.
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