Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Journal Sections
    • Subscriptions
    • Reviewing
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Collections
      • COVID-19 & Cancer Resource Center
      • Clinical Trials
      • Immuno-oncology
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
    • Journal Press Releases
  • COVID-19
  • Webinars
  • 10th Anniversary
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Discovery
Cancer Discovery
  • Home
  • About
    • The Journal
    • AACR Journals
    • Journal Sections
    • Subscriptions
    • Reviewing
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Collections
      • COVID-19 & Cancer Resource Center
      • Clinical Trials
      • Immuno-oncology
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
    • Journal Press Releases
  • COVID-19
  • Webinars
  • 10th Anniversary
  • Search More

    Advanced Search

Research Watch

HOXA5 Promotes Differentiation by Reducing WNT Signaling

DOI: 10.1158/2159-8290.CD-RW2015-240 Published February 2016
  • Article
  • Info & Metrics
Loading
  • Major finding: HOXA5 and WNT negatively regulate each other to control stem cell maintenance and differentiation.

  • Concept: HOXA5-induced differentiation of colon cancer stem cells inhibits tumor progression and metastasis.

  • Impact: Retinoids may effectively treat colon cancer by inducing HOXA5 and promoting terminal differentiation.

In colorectal cancer, a small population of self-renewing cancer stem cells (CSC) is an important driver of metastasis and is more resistant to treatment than differentiated cells. In normal intestinal epithelium, WNT/β-catenin signaling controls the maintenance of the stem cell population. In order to identify potential therapeutic strategies to target colorectal CSCs, Ordóñez-Morán and colleagues investigated the role of WNTs in maintaining their stem-cell properties. In normal intestinal epithelium, genetic ablation of WNT signaling promoted the terminal differentiation of stem cells, and transcriptional profiling determined that homeobox A5 (HOXA5) expression was inversely correlated with WNT signaling and expression of WNT target genes. HOXA5 inhibited intestinal stem cell maintenance and was required for terminal differentiation. In a human colon cancer dataset, HOXA5 expression was lower in carcinoma than in normal colon tissue, and high HOXA5 expression was an independent prognostic factor predicting improved relapse-free survival. WNT signaling suppressed HOXA5 expression indirectly via WNT-mediated upregulation of MYC and repression by the MYC–MIZ1 complex. Stable expression of HOXA5 in colon cancer cell lines promoted terminal differentiation and overcame WNT-driven transformation, suggesting inhibition of stem-cell traits, and, in vivo, HOXA5 reduced the growth and metastatic progression of tumor xenografts. In addition, HOXA5 reciprocally repressed WNT signaling, providing a mechanism by which HOXA5 inhibits the stem cell phenotype. Treatment of colon cancer cells with retinoids such as all-trans retinoic acid, which have been shown to upregulate HOXA5 in breast cancer, promoted CSC differentiation and blocked colon cancer initiation, progression, and metastasis via HOXA5 induction. These results demonstrate that WNT and HOXA5 negatively regulate each other to control tumor cell differentiation, and suggest that retinoids may have promise in treating colorectal cancer by promoting loss of the CSC phenotype.

Ordóñez-Morán P, Dafflon C, Imajo M, Nishida E, Huelsken J. HOXA5 counteracts stem cell traits by inhibiting Wnt signaling in colorectal cancer. Cancer Cell 2015;28:815–29.

  • ©2015 American Association for Cancer Research.
PreviousNext
Back to top
Cancer Discovery: 6 (2)
February 2016
Volume 6, Issue 2
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover

Sign up for alerts

View this article with LENS

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Discovery article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
HOXA5 Promotes Differentiation by Reducing WNT Signaling
(Your Name) has forwarded a page to you from Cancer Discovery
(Your Name) thought you would be interested in this article in Cancer Discovery.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
HOXA5 Promotes Differentiation by Reducing WNT Signaling
Cancer Discov February 1 2016 (6) (2) OF9; DOI: 10.1158/2159-8290.CD-RW2015-240

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
HOXA5 Promotes Differentiation by Reducing WNT Signaling
Cancer Discov February 1 2016 (6) (2) OF9; DOI: 10.1158/2159-8290.CD-RW2015-240
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Research Watch

  • Structures Identify Selpercatinib and Pralsetinib Resistance Mechanisms
  • Cryo-EM Structures Reveal Mechanism of Anticancer MCT1 Inhibitors
  • Computational Tool Characterizes Previously Unidentified Tumor Subtypes
Show more Research Watch

Stem Cells

  • CXCL12 Has Niche-Specific Roles in Leukemia Stem Cell Function
  • CD10+GPR77+ Cancer-Associated Fibroblasts Promote Chemoresistance
  • LGR5+ Cancer Stem Cells Drive Primary and Metastatic Colorectal Cancer
Show more Stem Cells
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • OnlineFirst
  • Current Issue
  • Past Issues

Info For

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Discovery

  • About the Journal
  • Editors
  • Journal Sections
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Discovery
eISSN: 2159-8290
ISSN: 2159-8274

Advertisement