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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche
Sato, T., Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., et al. (2009) · Nature · doi:10.1038/nature07935 · Cited by 7,204
Identification of stem cells in small intestine and colon by marker gene Lgr5
Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687
A human colon cancer cell capable of initiating tumour growth in immunodeficient mice
O'Brien, C. A., Pollett, A. F., Gallinger, S., & Dick, J. E. (2006) · Nature · doi:10.1038/nature05372 · Cited by 4,174
Identification and expansion of human colon-cancer-initiating cells
Ricci‐Vitiani, L., Lombardi, D. G., Pilozzi, E., Biffoni, M., Todaro, M., Peschle, C., & Maria, R. D. (2006) · Nature · doi:10.1038/nature05384 · Cited by 4,001
The Genomic Landscapes of Human Breast and Colorectal Cancers
Wood, L. D., Parsons, D. W., Jones, S., Lin, J., Sjöblom, T., Leary, R. J., Shen, D., Boca, S. M., Barber, T., Ptak, J., et al. (2007) · Science · doi:10.1126/science.1145720 · Cited by 2,833
Wnt proteins are lipid-modified and can act as stem cell growth factors
Willert, K., Brown, J. D., Danenberg, E., Duncan, A. W., Weissman, I. L., Reya, T., Yates, J. R., & Nusse, R. (2003) · Nature · doi:10.1038/nature01611 · Cited by 2,257
The β-Catenin/TCF-4 Complex Imposes a Crypt Progenitor Phenotype on Colorectal Cancer Cells
van de Wetering, M., Sancho, E., Verweij, C., de Lau, W., Oving, I., Hurlstone, A., van der Horn, K., Batlle, E., Coudreuse, D., Haramis, A.-P., et al. (2002) · Cell · doi:10.1016/s0092-8674(02)01014-0 · Cited by 2,030
WNT signalling pathways as therapeutic targets in cancer
Anastas, J. N., & Moon, R. T. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3419 · Cited by 1,945
Flagged first, then by citations
1 of the 73 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 201–219 of 219
Vangala, D., Ladigan, S., Liffers, S. T., Noseir, S., Maghnouj, A., Götze, T.-M., Verdoodt, B., Klein‐Scory, S., Godfrey, L., Zowada, M. K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14998919
Vangala, D., Ladigan, S., Liffers, S. T., Noseir, S., Maghnouj, A., Götze, T.-M., Verdoodt, B., Klein‐Scory, S., Godfrey, L., Zowada, M. K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14998901
Vangala, D., Ladigan, S., Liffers, S. T., Noseir, S., Maghnouj, A., Götze, T.-M., Verdoodt, B., Klein‐Scory, S., Godfrey, L., Zowada, M. K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14998910
Lin, R., Li, C., Liu, Z., Wu, R., & Lu, J. (2020) · Figshare · doi:10.6084/m9.figshare.12750026
Lin, R., Li, C., Liu, Z., Wu, R., & Lu, J. (2020) · Figshare · doi:10.6084/m9.figshare.12750023
Vangala, D., Ladigan, S., Liffers, S. T., Noseir, S., Maghnouj, A., Götze, T.-M., Verdoodt, B., Klein‐Scory, S., Godfrey, L., Zowada, M. K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14998925
Lin, R., Li, C., Liu, Z., Wu, R., & Lu, J. (2020) · Figshare · doi:10.6084/m9.figshare.12750035
Lin, R., Li, C., Liu, Z., Wu, R., & Lu, J. (2020) · Figshare · doi:10.6084/m9.figshare.12750032
Vangala, D., Ladigan, S., Liffers, S. T., Noseir, S., Maghnouj, A., Götze, T.-M., Verdoodt, B., Klein‐Scory, S., Godfrey, L., Zowada, M. K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14998916
Vangala, D., Ladigan, S., Liffers, S. T., Noseir, S., Maghnouj, A., Götze, T.-M., Verdoodt, B., Klein‐Scory, S., Godfrey, L., Zowada, M. K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14998913
Kumar, P., Slaven, J. E., Zhou, T., Tran, M. T., & Shields, M. D. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5413619
Vangala, D., Ladigan, S., Liffers, S. T., Noseir, S., Maghnouj, A., Götze, T.-M., Verdoodt, B., Klein‐Scory, S., Godfrey, L., Zowada, M. K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14998907
Lin, R., Li, C., Liu, Z., Wu, R., & Lu, J. (2020) · Figshare · doi:10.6084/m9.figshare.12750017
Abdelsalam, H. M., Abdelghany, A. M., Ahmed, W. A., Diab, A. A., & Abdellateif, M. S. (2025) · World Journal of Experimental Medicine · doi:10.5493/wjem.v15.i4.110757
Kumar, P., Slaven, J. E., Zhou, T., Tran, M. T., & Shields, M. D. (2026) · Clinical Lung Cancer · doi:10.1016/j.cllc.2026.03.014
Boiteux, E. L. (2019) · theses.fr (ABES) · doi:10.70675/fd2f33cazc6a6z47b4z8258zac9ac2e67e38
Kisling, S. G., Shah, A., Johnson, E., Alsafwani, Z. W., Raman, V., & Batra, S. K. (2026) · Cancer and Metastasis Reviews · doi:10.1007/s10555-026-10338-x
Zhang, J., Wu, Q., Liu, J., & Li, S. (2026) · Cancer Gene Therapy · doi:10.1038/s41417-026-01062-3
Sun, Q., Xu, H., Yang, S., Zhou, J., Tian, C., Nie, H., Jin, C., Wang, T., Chen, Z., Tang, J., et al. (2026) · Advanced Science · doi:10.1002/advs.76992
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
