Abstract 4287: Peroxiredoxin 2 has a crucial role in the survival of gastric cancer cells by regulating β-catenin and TNF signaling

• Published in: Cancer research (Chicago, Ill.) Ill.), 2019-07, Vol.79 (13_Supplement), p.4287-4287
• Main Authors: Kim, Hee Sung, Lee, Tae Hyeong, Kang, Dong Hoon, Lee, Peter Chang-Whan, Kim, Byung Sik
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2019-4287

Gastric cancer (GC) is globally the fifth most common cancer and third leading cause of cancer death. Functional activation of β-catenin is necessary for early events in gastric carcinogenesis and GC with mutation of APC gene, similar to colorectal tumorigenesis, occur during the early stages of gastric adenoma development. Mammalian 2-Cys peroxiredoxin (Prx) enzymes are overexpressed in most cancer tissues, but the effect of Prx2 expression on GC survival remains unclear. Here, we demonstrate that Prx2 deletion markedly reduces the active β-catenin levels and the expression of β-catenin target genes in GC cells. Furthermore, the TNF α-induced activation of ERK1/2 was inhibited and reciprocally, JNK phosphorylation and cleaved caspase3 was increased in Prx2-knockdown GC cells. Prx2 deletion also can suppress the viability, invasion and colony formation of GC cells. The proof-of-concept experiment using conoidinA as a Prx2 inhibitor shows it can significantly ablates the growth of 5-FU-resistant SNU620. Thus, our findings reveal that Prx2 is a key regulator of β-catenin and TNF signaling pathway in GC, and also suggest a pharmacologic strategy to effectively overcome drug-resistant GC. Note: This abstract was not presented at the meeting. Citation Format: Hee Sung Kim, Tae Hyeong Lee, Dong Hoon Kang, Peter Chang-Whan Lee, Byung Sik Kim. Peroxiredoxin 2 has a crucial role in the survival of gastric cancer cells by regulating β-catenin and TNF signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4287.