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

Dong Hoon Kang, Doo Jae Lee, Sunmi Lee, So Young Lee, Yukyung Jun, Yerin Kim, Youngeun Kim, Ju Seog Lee, Dae Kee Lee, Sanghyuk Lee, Eek Hoon Jho, Dae Yeul Yu, Sang Won Kang

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37 Scopus citations


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.

Original languageEnglish
Article number40
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2017

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