ONECUT2-driven activation of ADAMTS14 boosts colorectal cancer stemness via Wnt pathway

The malignant progression of colorectal cancer (CRC) is closely related to cell stemness, but its regulatory mechanism has not been fully elucidated. This study found that ADAMTS14 was significantly highly expressed in CRC tissues and cell lines and was associated with poor prognosis in patients. Fu...

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Bibliographic Details
Published in:Human cell : official journal of Human Cell Research Society Vol. 39; no. 1; p. 7
Main Authors: Jiang, Yicheng, Tan, Xingping
Format: Journal Article
Language:English
Published: Japan Springer Nature B.V 12.11.2025
Subjects:
ADAMTS Proteins - genetics
ADAMTS Proteins - metabolism
Bioinformatics
Cell Line, Tumor
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Gene Expression Regulation, Neoplastic - genetics
Humans
Liver cancer
Medical prognosis
Metastasis
Mortality
Neoplastic Stem Cells - pathology
Penicillin
Plasmids
Prognosis
Signal transduction
Stem cells
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription Factors - physiology
Treatment resistance
Wnt protein
Wnt Signaling Pathway - genetics
United States > US
China
Germany
ADAMTS14
Cell stemness
Wnt signaling pathway
ONECUT2
Colorectal cancer
ISSN:1749-0774, 0914-7470, 1749-0774
Online Access:Get full text
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Summary:The malignant progression of colorectal cancer (CRC) is closely related to cell stemness, but its regulatory mechanism has not been fully elucidated. This study found that ADAMTS14 was significantly highly expressed in CRC tissues and cell lines and was associated with poor prognosis in patients. Functional experiments have confirmed that ADAMTS14 enhances the stemness characteristics (such as upregulation of ALDH1A1, ALDH1A3, and CD133 expression) and spheroidization ability of CRC cells by activating the Wnt signaling pathway. Further mechanism studies have shown that the transcription factor ONECUT2 is also highly expressed in CRC and indicates a poor prognosis, and it can directly activate its transcription by binding to the ADAMTS14 promoter region. In conclusion, this study has revealed a novel mechanism by which the ONECUT2/ADAMTS14/Wnt axis regulates the stemness of CRC cells, providing a potential molecular target for targeted intervention.
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ISSN:1749-0774
0914-7470
1749-0774
DOI:10.1007/s13577-025-01319-3