KY1022, a Small Molecule Destabilizing Ras Via Targeting the Wnt/β-catenin Pathway, Inhibits Development of Metastatic Colorectal Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Nov 12

PMID 27835580

Citations 24

Authors

Yong-Hee Cho

Pu-Hyeon Cha

Saluja Kaduwal

Jong-Chan Park

Sang-Kyu Lee

Jeong-Soo Yoon

Wookjin Shin

Hyuntae Kim

Eun Ji Ro

Kyung-Hwa Koo

Ki-Sook Park

Gyoonhee Han

Kang-Yell Choi

Affiliations

Soon will be listed here.

Abstract

APC (80-90%) and K-Ras (40-50%) mutations frequently occur in human colorectal cancer (CRC) and these mutations cooperatively accelerate tumorigenesis including metastasis. In addition, both β-catenin and Ras levels are highly increased in CRC, especially in metastatic CRC (mCRC). Therefore, targeting both the Wnt/β-catenin and Ras pathways could be an ideal therapeutic approach for treating mCRC patients. In this study, we characterized the roles of KY1022, a small molecule that destabilizes both β-catenin and Ras via targeting the Wnt/β-catenin pathway, in inhibiting the cellular events, including EMT, an initial process of metastasis, and apoptosis. As shown by in vitro and in vivo studies using APCMin/+/K-RasG12DLA2 mice, KY1022 effectively suppressed the development of mCRC at an early stage of tumorigenesis. A small molecular approach degrading both β-catenin and Ras via inhibition of the Wnt/β-catenin signaling would be an ideal strategy for treatment of mCRC.

Citing Articles

API-2-Induced Cell Migration Is Overcome by Small Molecular Approaches Inhibiting β-Catenin.

Kim Y, Kang M, Cho Y Curr Issues Mol Biol. 2022; 44(12):6006-6014.

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Potential Role of Traditional Chinese Medicines by Wnt/β-Catenin Pathway Compared With Targeted Small Molecules in Colorectal Cancer Therapy.

Chang J, Xavier H, Chen D, Liu Y, Li H, Bian Z Front Pharmacol. 2021; 12:690501.

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Post-translational modification of RAS proteins.

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