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Peroxiredoxin-1 Tyr194 phosphorylation regulates LOX-dependent extracellular matrix remodelling in breast cancer

Title
Peroxiredoxin-1 Tyr194 phosphorylation regulates LOX-dependent extracellular matrix remodelling in breast cancer
Authors
Attaran S.Skoko J.J.Hopkins B.L.Wright M.K.Wood L.E.Asan A.Woo H.A.Feinberg A.Neumann C.A.
Ewha Authors
우현애
SCOPUS Author ID
우현애scopus
Issue Date
2021
Journal Title
British Journal of Cancer
ISSN
0007-0920JCR Link
Citation
British Journal of Cancer vol. 125, no. 8, pp. 1146 - 1157
Publisher
Springer Nature
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Background: Peroxiredoxin 1 (PRDX1) belongs to an abundant family of peroxidases whose role in cancer is still unresolved. While mouse knockout studies demonstrate a tumour suppressive role for PRDX1, in cancer cell xenografts, results denote PRDX1 as a drug target. Probably, this phenotypic discrepancy stems from distinct roles of PRDX1 in certain cell types or stages of tumour progression. Methods: We demonstrate an important cell-autonomous function for PRDX1 utilising a syngeneic mouse model (BALB/c) and mammary fibroblasts (MFs) obtained from it. Results: Loss of PRDX1 in vivo promotes collagen remodelling known to promote breast cancer progression. PRDX1 inactivation in MFs occurs via SRC-induced phosphorylation of PRDX1 TYR194 and not through the expected direct oxidation of CYS52 in PRDX1 by ROS. TYR194-phosphorylated PRDX1 fails to bind to lysyl oxidases (LOX) and leads to the accumulation of extracellular LOX proteins which supports enhanced collagen remodelling associated with breast cancer progression. Conclusions: This study reveals a cell type-specific tumour suppressive role for PRDX1 that is supported by survival analyses, depending on PRDX1 protein levels in breast cancer cohorts. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
DOI
10.1038/s41416-021-01510-x
Appears in Collections:
약학대학 > 약학과 > Journal papers
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