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

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

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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Crossref · 10.1016/j.ccell.2015.11.001

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  • De-differentiation is exemplified by colon carcinogenesis due to loss of HOXA5 and SMAD4, melanomagenesis due to loss of MITF, and pancreatic neuroendocrine tumors due to loss of a differentiation-inducing miRNA in beta cells.

    “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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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
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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