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Survival of APC-mutant colorectal cancer cells requires interaction between tankyrase and a thiol peroxidase, peroxiredoxin II

Title
Survival of APC-mutant colorectal cancer cells requires interaction between tankyrase and a thiol peroxidase, peroxiredoxin II
Authors
Kang, Dong HoonLee, Joanna H. S.Kang, Sang Won
Ewha Authors
강상원
SCOPUS Author ID
강상원scopus
Issue Date
2017
Journal Title
BMB REPORTS
ISSN
1976-6696JCR Link1976-670XJCR Link
Citation
vol. 50, no. 8, pp. 391 - 392
Keywords
AxinColorectal cancerPeroxiredoxinTankyrasebeta-catenin
Publisher
KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
Indexed
SCIE; SCOPUS; KCI WOS
Abstract
Overexpression of mammalian 2-Cys peroxiredoxin (Prx) enzymes is observed in most cancer tissues. Nevertheless, their specific roles in colorectal cancer (CRC) progression has yet to be fully elucidated. Here, a novel molecular mechanism by which PrxII/Tankyrase (TNKS) interaction mediates survival of adenomatous polyposis coli (APC)-mutant CRC cells was explored. In mice with an inactivating APC mutation, a model of spontaneous intestinal tumorigenesis, deletion of PrxII reduced intestinal adenomatous polyposis and thereby increased survival. In APC-mutant human CRC cells, PrxII depletion hindered PARP-dependent Axin1 degradation through TNKS inactivation. H2O2-sensitive Cys residues in the zinc-binding domain of TNKS1 was found to be crucial for PARsylation activity. Mechanistically, direct binding of PrxII to ARC4/5 domains of TNKS conferred vital redox protection against oxidative inactivation. As a proof-of-concept experiment, a chemical compound targeting PrxII inhibited the growth of tumors xenografted with APC-mutation-positive CRC cells. Collectively, the results provide evidence revealing a novel redox mechanism for regulating TNKS activity such that physical interaction between PrxII and TNKS promoted survival of APC-mutant colorectal cancer cells by PrxII-dependent antioxidant shielding.
DOI
10.5483/BMBRep.2017.50.8.120
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자연과학대학 > 생명과학전공 > Journal papers
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