Small molecule-induced simultaneous destabilization of β-catenin and RAS is an effective molecular strategy to suppress stemness of colorectal cancer cells.

Cell Communication and Signaling : CCS
Yong-Hee ChoKang-Yell Choi

Abstract

Cancer stem cells (CSCs), the major driver of tumorigenesis, is a sub-population of tumor cells responsible for poor clinical outcomes. However, molecular mechanism to identify targets for controlling CSCs is poorly understood. Gene Set Enrichment Analyses (GSEA) of Wnt/β-catenin and RAS signaling pathways in stem-like subtype of colorectal cancer (CRC) patients were performed using two gene expression data set. The therapeutic effects of destabilization of β-catenin and RAS were tested by treatment of small molecule KYA1797K using CRC patient derived cells. Treatment with KYA1797K, a small molecule that destabilizes both β-catenin and RAS via Axin binding, effectively suppresses the stemness of CSCs as shown in CRC spheroids and small intestinal tumors of ApcMin/+/K-RasG12DLA2 mice. Moreover, KYA1797K also suppresses the stemness of cells in CRC patient avatar model systems, such as patient-derived tumor organoids (PDTOs) and patient-derived tumor xenograft (PDTX). Our results suggest that destabilization of both β-catenin and RAS is a potential therapeutic strategy for controlling stemness of CRC cells. Video abstract.

References

Mar 1, 1996·Molecular and Cellular Biology·G M D'AbacoA W Burgess
Sep 6, 2007·Molecular and Cellular Biology·Tea FevrJoerg Huelsken
Oct 13, 2007·Science·Laura D WoodBert Vogelstein
Dec 19, 2008·Nature·Nick BarkerHans Clevers
Apr 13, 2012·Science Signaling·Daniele Guardavaccaro, Hans Clevers
Jun 27, 2013·World Journal of Gastrointestinal Oncology·Kypros Zenonos, Katy Kyprianou
Feb 5, 2014·Journal of the National Cancer Institute·Byoung-San MoonKang-Yell Choi
Oct 11, 2014·Cell Death and Differentiation·M SchmittV Orian-Rousseau
Jun 14, 2016·Nature Chemical Biology·Pu-Hyeon ChaKang-Yell Choi
Jul 16, 2016·Scientific Reports·Matias RiihimäkiKari Hemminki
Sep 2, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hye-Young MinHo-Young Lee
Mar 31, 2017·Nature·Felipe de Sousa e MeloFrederic J de Sauvage
Sep 25, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dong Woo KangDo Sik Min
Oct 7, 2017·Nature Medicine·Eduard Batlle, Hans Clevers
Oct 10, 2018·Nature·Adriana Sánchez-DanésCédric Blanpain
Aug 1, 2019·Cell Communication and Signaling : CCS·Eun Ji RoKang-Yell Choi

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Citations

Oct 22, 2020·International Journal of Molecular Sciences·Malvina KoniMaria Felice Brizzi
Feb 27, 2021·British Journal of Pharmacology·Fiona M HealyDavid J MacEwan

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Datasets Mentioned

BETA
GSE14333
N

Methods Mentioned

BETA
xenograft
PCR
genotyping
Assay
FACS

Software Mentioned

Image J
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