Small molecule-induced simultaneous destabilization of ß-catenin and RAS is an effective molecular strategy to suppress stemness of colorectal cancer cells.
Cell Commun Signal
; 18(1): 38, 2020 03 06.
Article
in En
| MEDLINE
| ID: mdl-32143715
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/ß-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 ß-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 ß-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 ß-catenin and RAS is a potential therapeutic strategy for controlling stemness of CRC cells. Video abstract.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Proto-Oncogene Proteins p21(ras)
/
Beta Catenin
/
Thiazolidines
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Carcinogenesis
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Commun Signal
Year:
2020
Document type:
Article
Affiliation country:
South Korea