The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation
Open accessAbstract
5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective clinical outcomes for CRC patients. Here, we demonstrate that p53 promotes WNT3 transcription, leading to activation of the WNT/β-catenin pathway in ApcMin/+/Lgr5EGFP mice, CRC patient-derived tumor organoids (PDTOs) and patient-derived tumor cells (PDCs). Through this regulation, 5-FU induces activation and enrichment of cancer stem cells (CSCs) in the residual tumors, contributing to recurrence after treatment. Combinatorial treatment of a WNT inhibitor and 5-FU effectively suppresses the CSCs and reduces tumor regrowth after discontinuation of treatment. These findings indicate p53 as a critical mediator of 5-FU-induced CSC activation via the WNT/β-catenin signaling pathway and highlight the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for CRC patients.
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Targeting the Wnt/β-catenin signaling pathway in cancer
Zhang, Y., & Wang, X. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00990-3 · Cited by 1,431
Wnt signaling in colorectal cancer: Pathogenic role and therapeutic target
Zhao, H., Ming, T., Tang, S., Ren, S., Yang, H., Liu, M., Tao, Q., & Xu, H. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01616-7 · Cited by 857
Recent advances in targeted drug delivery systems for resistant colorectal cancer
Sharifi-Azad, M., Fathi, M., Cho, W. C., Barzegari, A., Dadashi, H., Dadashpour, M., & Jahanban-Esfahlan, R. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02605-y · Cited by 65
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Patient-derived tumor models: a more suitable tool for pre-clinical studies in colorectal cancer
Rizzo, G., Bertotti, A., Leto, S. M., & Vetrano, S. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01970-2 · Cited by 51
Metadata
- Authors
- Cho, Y.-H., Ro, E. J., Yoon, J.-S., Mizutani, T., Kang, D.-W., Park, J.-C., Il Kim, T., Clevers, H., & Choi, K.-Y.
- Venue
- Nature Communications
- Published
- 2020-10-21
- Volume
- 11
- Issue
- 1
- Pages
- 5321-5321
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W3094321390
- Cited by
- 336
- References
- 43
- FWCI
- 12.17
- Type
- journal article
- Language
- en
- Open access
- gold
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- Cho, Y.-H., Ro, E. J., Yoon, J.-S., Mizutani, T., Kang, D.-W., Park, J.-C., Il Kim, T., Clevers, H., & Choi, K.-Y. (2020). 5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation. Nature Communications. https://doi.org/10.1038/s41467-020-19173-2
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