Cited by 219Wnt/β-catenin signaling in development and cancerCancer Cells and MetastasisDevelopmental Biology and Gene Regulation

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HOXA5 Counteracts Stem Cell Traits by Inhibiting Wnt Signaling in Colorectal Cancer

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Ordóñez-Morán, Paloma, Dafflon, Caroline, Imajo, Masamichi, Nishida, Eisuke, Huelsken, Joerg·2015·Cancer Cell

DOI 10.1016/j.ccell.2015.11.001

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Abstract

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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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
ORCID: Imajo, Masamichi
Nishida, Eisuke
Huelsken, Joerg
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2015-12
Volume: 28
Issue: 6
Pages: 815-829
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccell.2015.11.001
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 379 d)
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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HOXA5 Counteracts Stem Cell Traits by Inhibiting Wnt Signaling in Colorectal Cancer

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