The DOI matches its Crossref record; 72 of the 73 references it cites were found in a registry or an index.
HOXA5 Counteracts Stem Cell Traits by Inhibiting Wnt Signaling in Colorectal Cancer
Open accessAbstract
Hierarchical organization of tissues relies on stem cells, which either self-renew or produce committed progenitors predestined for lineage differentiation. Here we identify HOXA5 as an important repressor of intestinal stem cell fate in vivo and identify a reciprocal feedback between HOXA5 and Wnt signaling. HOXA5 is suppressed by the Wnt pathway to maintain stemness and becomes active only outside the intestinal crypt where it inhibits Wnt signaling to enforce differentiation. In colon cancer, HOXA5 is downregulated, and its re-expression induces loss of the cancer stem cell phenotype, preventing tumor progression and metastasis. Tumor regression by HOXA5 induction can be triggered by retinoids, which represent tangible means to treat colon cancer by eliminating cancer stem cells.
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“De-differentiation is exemplified by colon carcinogenesis (due to the loss of the differentiation-inducing transcription factor HOXA5 and SMAD4), 141,142 melanomagenesis (due to the loss of the transcription factor MITF), 143 or pancreatic neuroendocrine tumors (due to the loss of a differentiation-inducing miRNA in b cells).144”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [142]
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Cited by
Sorted by citations
Hallmarks of Cancer: New Dimensions
Hanahan, D. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1059 · Cited by 9,887
Targeting cancer stem cell pathways for cancer therapy
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Meta-hallmarks of aging and cancer
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Drug repurposing for cancer therapy
Xia, Y., Sun, M., Huang, H., & Jin, W.-L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01808-1 · Cited by 443
“189 Exploiting these mechanisms through drug repurposing might offer novel groundbreaking therapeutic approaches.”
BackgroundWnt signaling pathways in biology and disease: mechanisms and therapeutic advances
Chen, X., Chu, Q., Shi, Q., Zeng, Y., Lu, J., & Li, J. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02142-w · Cited by 347
Metadata
- Authors
- Ordóñez-Morán, P., Dafflon, C., Imajo, M., Nishida, E., & Huelsken, J.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Kyoto University (JP)
- Corresponding author
- Huelsken, Joerg
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 28
- Issue
- 6
- Pages
- 815-829
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2189633061
- Cited by
- 209
- References
- 73
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 12 · 2023: 20 · 2022: 18 · 2021: 31 · 2020: 27 · 2019: 25 · 2018: 21 · 2017: 23 · 2016: 11 · 2015: 1
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Repository@Nottingham (University of Nottingham) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (25870363)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- HOXA5, Wnt signaling, colorectal cancer, cancer stem cells, intestinal stem cells, stemness, cell differentiation, retinoids, tumor regression, metastasis, tumor progression
- MeSH terms
- Aged, Aged, 80 and over, Animals, Antineoplastic Agents, Cell Differentiation, Cell Transformation, Neoplastic, Female, Humans, Intestinal Mucosa, Male, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Neoplasm Metastasis, Phenotype, Phosphoproteins, Retinoids, Time Factors, Transcription Factors, Transfection, Tumor Cells, Cultured, Neoplastic Stem Cells, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Homeodomain Proteins, Caco-2 Cells, HT29 Cells, Feedback, Physiological, RNA Interference, HCT116 Cells, Tissue Culture Techniques, Cell Proliferation, Wnt Signaling Pathway
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