| Literature DB >> 27294323 |
Pu-Hyeon Cha1,2, Yong-Hee Cho1,2, Sang-Kyu Lee1,2, JaeHeon Lee1,2, Woo-Jeong Jeong1,2, Byoung-San Moon1,2, Ji-Hye Yun1,3, Jee Sun Yang1,2, Sooho Choi1,3, Juyong Yoon1,2, Hyun-Yi Kim1,2, Mi-Yeon Kim1,2, Saluja Kaduwal1,2, Weontae Lee1,3, Do Sik Min1,4, Hoguen Kim5, Gyoonhee Han1,2, Kang-Yell Choi1,2.
Abstract
Both the Wnt/β-catenin and Ras pathways are aberrantly activated in most human colorectal cancers (CRCs) and interact cooperatively in tumor promotion. Inhibition of these signaling may therefore be an ideal strategy for treating CRC. We identified KY1220, a compound that destabilizes both β-catenin and Ras, via targeting the Wnt/β-catenin pathway, and synthesized its derivative KYA1797K. KYA1797K bound directly to the regulators of G-protein signaling domain of axin, initiating β-catenin and Ras degradation through enhancement of the β-catenin destruction complex activating GSK3β. KYA1797K effectively suppressed the growth of CRCs harboring APC and KRAS mutations, as shown by various in vitro studies and by in vivo studies using xenograft and transgenic mouse models of tumors induced by APC and KRAS mutations. Destabilization of both β-catenin and Ras via targeting axin is a potential therapeutic strategy for treatment of CRC and other type cancers activated Wnt/β-catenin and Ras pathways.Entities:
Mesh：
Substances：
Year: 2016 PMID： 27294323 DOI： 10.1038/nchembio.2103
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040