The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Apc Restoration Promotes Cellular Differentiation and Reestablishes Crypt Homeostasis in Colorectal Cancer
Open accessAbstract
The Adenomatous Polyposis Coli (APC) tumor suppressor is mutated in the vast majority of human colorectal cancers (CRC) and leads to deregulated Wnt signaling. To determine whether Apc disruption is required for tumor maintenance, we developed a mouse model of CRC whereby Apc can be conditionally suppressed using a doxycycline-regulated shRNA. Apc suppression produces adenomas in both the small intestine and colon that, in the presence of Kras and p53 mutations, can progress to invasive carcinoma. In established tumors, Apc restoration drives rapid and widespread tumor-cell differentiation and sustained regression without relapse. Tumor regression is accompanied by the re-establishment of normal crypt-villus homeostasis, such that once aberrantly proliferating cells reacquire self-renewal and multi-lineage differentiation capability. Our study reveals that CRC cells can revert to functioning normal cells given appropriate signals, and provide compelling in vivo validation of the Wnt pathway as a therapeutic target for treatment of CRC.
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Cites
Comprehensive molecular characterization of human colon and rectal cancer
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MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer
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Self-citationBroadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity
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Cited by
Zhan, T., Rindtorff, N., & Boutros, M. (2017) · Oncogene · doi:10.1038/onc.2016.304 · Cited by 2,626
Drost, J., & Clevers, H. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0007-6 · Cited by 1,790
Self-citationA rectal cancer organoid platform to study individual responses to chemoradiation
Ganesh, K., Wu, C., O’Rourke, K. P., Szeglin, B. C., Zheng, Y., Sauvé, C.-E. G., Adileh, M., Wasserman, I., Marco, M. R., Kim, A. S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0584-2 · Cited by 569
Self-citationGenetically engineered mouse models in oncology research and cancer medicine
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Mutations and mechanisms of WNT pathway tumour suppressors in cancer
Bugter, J. M., Fenderico, N., & Maurice, M. M. (2021) · Nature Reviews Cancer · doi:10.1038/s41568-020-00307-z · Cited by 466
Metadata
- Authors
- Dow, L. E., O’Rourke, K. P., Simon, J., Tschaharganeh, D. F., van Es, J. H., Clevers, H., & Lowe, S. W.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 161
- Issue
- 7
- Pages
- 1539-1552
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1655178001
- Cited by
- 552
- References
- 9
- FWCI
- 20.46
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Dow, L. E., O’Rourke, K. P., Simon, J., Tschaharganeh, D. F., van Es, J. H., Clevers, H., & Lowe, S. W. (2015). Apc Restoration Promotes Cellular Differentiation and Reestablishes Crypt Homeostasis in Colorectal Cancer. Cell. https://doi.org/10.1016/j.cell.2015.05.033
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