View : 72 Download: 8

Interaction of tankyrase and peroxiredoxin II is indispensable for the survival of colorectal cancer cells

Title
Interaction of tankyrase and peroxiredoxin II is indispensable for the survival of colorectal cancer cells
Authors
Kang D.H.Lee D.J.Lee S.Lee S.-Y.Jun Y.Kim Y.Lee J.-S.Lee D.-K.Jho E.-H.Yu D.-Y.Kang S.W.
Ewha Authors
이상혁강상원이대기이두재강동훈
SCOPUS Author ID
이상혁scopus; 강상원scopus; 이대기scopus; 이두재scopus; 강동훈scopus
Issue Date
2017
Journal Title
Nature Communications
ISSN
2041-1723JCR Link
Citation
vol. 8, no. 1
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Mammalian 2-Cys peroxiredoxin (Prx) enzymes are overexpressed in most cancer tissues, but their specific signaling role in cancer progression is poorly understood. Here we demonstrate that Prx type II (PrxII) plays a tumor-promoting role in colorectal cancer by interacting with a poly(ADP-ribose) polymerase (PARP) tankyrase. PrxII deletion in mice with inactivating mutation of adenomatous polyposis coli (APC) gene reduces intestinal adenomatous polyposis via Axin/β-catenin axis and thereby promotes survival. In human colorectal cancer cells with APC mutations, PrxII depletion consistently reduces the β-catenin levels and the expression of β-catenin target genes. Essentially, PrxII depletion hampers the PARP-dependent Axin1 degradation through tankyrase inactivation. Direct binding of PrxII to tankyrase ARC4/5 domains seems to be crucial for protecting tankyrase from oxidative inactivation. Furthermore, a chemical compound targeting PrxII inhibits the expansion of APC-mutant colorectal cancer cells in vitro and in vivo tumor xenografts. Collectively, this study reveals a redox mechanism for regulating tankyrase activity and implicates PrxII as a targetable antioxidant enzyme in APC-mutation-positive colorectal cancer. © The Author(s) 2017.
DOI
10.1038/s41467-017-00054-0
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
Files in This Item:
Interaction of tankyrase.pdf(3.06 MB)Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE