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

Ord��ez-Mor�n, Paloma; Dafflon, Caroline; Imajo, Masamichi; Nishida, Eisuke; Huelsken, Joerg

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.

Citation

Ordóñez-Morán, P., Dafflon, C., Imajo, M., Nishida, E., & Huelsken, J. (2015). HOXA5 Counteracts Stem Cell Traits by Inhibiting Wnt Signaling in Colorectal Cancer. Cancer Cell, 28(6), 815-829. https://doi.org/10.1016/j.ccell.2015.11.001

• Journal Article Type: Article
• Acceptance Date: Nov 5, 2015
• Online Publication Date: Dec 14, 2015
• Publication Date: Dec 14, 2015
• Deposit Date: Jan 15, 2021
• Journal: Cancer Cell
• Print ISSN: 1535-6108
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 28
• Issue: 6
• Pages: 815-829
• DOI: https://doi.org/10.1016/j.ccell.2015.11.001
• Keywords: Cell Biology; Cancer Research; Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/5228974
• Publisher URL: https://www.cell.com/cancer-cell/fulltext/S1535-6108(15)00422-5
• Related Public URLs: https://www.sciencedirect.com/science/article/pii/S1535610815004225
• Additional Information: This article is maintained by: Elsevier; Article Title: HOXA5 Counteracts Stem Cell Traits by Inhibiting Wnt Signaling in Colorectal Cancer; Journal Title: Cancer Cell; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ccell.2015.11.001; CrossRef DOI link to the associated document: https://doi.org/10.1016/j.ccell.2015.11.004; Content Type: article; Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.