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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
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Cho, Yong-Hee | - |
dc.contributor.author | Ro, Eun Ji | - |
dc.contributor.author | Yoon, Jeong-Su | - |
dc.contributor.author | Kwak, Dong-Kyu | - |
dc.contributor.author | Cho, Jaebeom | - |
dc.contributor.author | Kang, Dong Woo | - |
dc.contributor.author | Lee, Ho-Young | - |
dc.contributor.author | Choi, Kang-Yell | - |
dc.date.accessioned | 2020-08-18T02:09:31Z | - |
dc.date.available | 2020-08-18T11:10:54Z | - |
dc.date.issued | 2020-03-06 | - |
dc.identifier.citation | Cell Communication and Signaling. 2020 Mar 06;18(1):38 | ko_KR |
dc.identifier.issn | 1478-811X | - |
dc.identifier.uri | https://hdl.handle.net/10371/168727 | - |
dc.description.abstract | Background
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.sponsorship | This 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.iso | en | ko_KR |
dc.publisher | BMC | ko_KR |
dc.subject | Cancer stem cells | - |
dc.subject | β-Catenin | - |
dc.subject | RAS | - |
dc.subject | Destabilization | - |
dc.subject | KYA1797K | - |
dc.title | Small molecule-induced simultaneous destabilization of β-catenin and RAS is an effective molecular strategy to suppress stemness of colorectal cancer cells | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 조용희 | - |
dc.contributor.AlternativeAuthor | 노은지 | - |
dc.contributor.AlternativeAuthor | 윤정수 | - |
dc.contributor.AlternativeAuthor | 조재범 | - |
dc.contributor.AlternativeAuthor | 강동우 | - |
dc.contributor.AlternativeAuthor | 이호영 | - |
dc.identifier.doi | doi.org/10.1186/s12964-020-0519-z | - |
dc.citation.journaltitle | Cell Communication and Signaling | ko_KR |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s). | - |
dc.date.updated | 2020-06-17T13:11:11Z | - |
dc.citation.number | 1 | ko_KR |
dc.citation.startpage | 38 | ko_KR |
dc.citation.volume | 18 | ko_KR |
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