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

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dc.contributor.authorCho, Yong-Hee-
dc.contributor.authorRo, Eun Ji-
dc.contributor.authorYoon, Jeong-Su-
dc.contributor.authorKwak, Dong-Kyu-
dc.contributor.authorCho, Jaebeom-
dc.contributor.authorKang, Dong Woo-
dc.contributor.authorLee, Ho-Young-
dc.contributor.authorChoi, Kang-Yell-
dc.date.accessioned2020-08-18T02:09:31Z-
dc.date.available2020-08-18T11:10:54Z-
dc.date.issued2020-03-06-
dc.identifier.citationCell Communication and Signaling. 2020 Mar 06;18(1):38ko_KR
dc.identifier.issn1478-811X-
dc.identifier.urihttps://hdl.handle.net/10371/168727-
dc.description.abstractBackground
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.

Methods
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.

Results
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).

Conclusion
Our results suggest that destabilization of both β-catenin and RAS is a potential therapeutic strategy for controlling stemness of CRC cells.
ko_KR
dc.description.sponsorshipThis work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIP) (grants 2016R1A5A1004694, 2019R1A2C3002751, 2018R1D1A1B07050189).ko_KR
dc.language.isoenko_KR
dc.publisherBMCko_KR
dc.subjectCancer stem cells-
dc.subjectβ-Catenin-
dc.subjectRAS-
dc.subjectDestabilization-
dc.subjectKYA1797K-
dc.titleSmall molecule-induced simultaneous destabilization of β-catenin and RAS is an effective molecular strategy to suppress stemness of colorectal cancer cellsko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor조용희-
dc.contributor.AlternativeAuthor노은지-
dc.contributor.AlternativeAuthor윤정수-
dc.contributor.AlternativeAuthor조재범-
dc.contributor.AlternativeAuthor강동우-
dc.contributor.AlternativeAuthor이호영-
dc.identifier.doidoi.org/10.1186/s12964-020-0519-z-
dc.citation.journaltitleCell Communication and Signalingko_KR
dc.language.rfc3066en-
dc.rights.holderThe Author(s).-
dc.date.updated2020-06-17T13:11:11Z-
dc.citation.number1ko_KR
dc.citation.startpage38ko_KR
dc.citation.volume18ko_KR
Appears in Collections:
College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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