Evidence map›Paper›PMID 23474758›Full record

ArticleOncogene2014

AXL induces epithelial-to-mesenchymal transition and regulates the function of breast cancer stem cells.

M K Asiedu, F D Beauchamp-Perez, J N Ingle, M D Behrens, D C Radisky, K L Knutson

Abstract read
In one paragraph

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers.

0numbers the graph read from it
0cells of the map it votes in
170citing papers in PubMed
10.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

170 citing papers in PubMed, 290 citations in OpenAlex.

  1. Review
  2. Article
  3. TheCells · 2026
    Article
  4. C3Journal of translational medicine · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Life Factors and Melanoma: From the Macroscopic State to the Molecular Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Novel Therapeutic Development for Nasopharyngeal Carcinoma.Current oncology (Toronto, Ont.) · 2025
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Navigating TAM receptor dynamics in tumour immunotherapy.Cancer immunology, immunotherapy : CII · 2025
    Review
  20. AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025
    Review

110 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

M K AsieduDepartment of Immunology, College of Medicine, Mayo Clinic, Rochester, MN, USA.
F D Beauchamp-PerezDepartment of Immunology, College of Medicine, Mayo Clinic, Rochester, MN, USA.
J N IngleDepartment of Oncology, College of Medicine, Mayo Clinic, Rochester, MN, USA.
M D BehrensDepartment of Immunology, College of Medicine, Mayo Clinic, Rochester, MN, USA.
D C RadiskyDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL, USA.
K L KnutsonDepartment of Immunology, College of Medicine, Mayo Clinic, Rochester, MN, USA.
Mayo Clinic · USWinnMed · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
MAYO CLINIC CENTER FOR TRANSLATIONAL SCIENCE ACTIVITIESUL1RR024150 · NCRR · MAYO CLINIC ROCHESTER · PI RIZZA, ROBERT A. · 2006 to 2011
$66.4M
The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9M
Mechanisms of MMP-Induced Malignancy in Breast CellsR01CA122086 · NCI · MAYO CLINIC JACKSONVILLE · PI RADISKY, DEREK C · 2007 to 2011
$1.4M
Ex vivo expansion of HER-2/neu specific T helper cellsK01CA100764 · NCI · UNIVERSITY OF WASHINGTON · PI KNUTSON, KEITH L. · 2004 to 2008
$742k
NCI NIH HHS K01 CA100764NCI NIH HHS K01-CA100764NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA116201NCI NIH HHS P50-CA116201NCI NIH HHS R01 CA122086NCI NIH HHS R01-CA122086NCRR NIH HHS UL1 RR024150
6 · The paper itself

Abstract

Despite significant progress in the treatment of breast cancer, particularly through the use of targeted therapy, relapse and chemoresistance remain a major hindrance to the fight to minimize the burden of the disease. It is becoming increasingly clear that a rare subpopulation of cells known as cancer stem cells (CSC), able to be generated through epithelial-to-mesenchymal transition (EMT) and capable of tumor initiation and self-renewal, contributes to treatment resistance and metastases. This means that a more effective therapy should target both the chemoresistant CSCs and the proliferating epithelial cells that give rise to them to reverse EMT and to attenuate their conversion to CSCs. Here, we demonstrate a novel function of AXL in acting upstream to induce EMT in normal and immortalized human mammary epithelial cells in an apparent positive feedback loop mechanism and regulate breast CSC (BCSC) self-renewal and chemoresistance. Downregulation of AXL using MP470 (Amuvatinib) reversed EMT in mesenchymal normal human mammary epithelial cells and murine BCSCs attenuating self-renewal and restored chemosensitivity of the BCSCs. AXL expression was also found to be associated with the expression of stem cell genes, regulation of metastases genes, increased tumorigenicity and was important for BCSC invasion and migration. Inactivation of AXL also led to the downregulation of nuclear factor-κB pathway and reduced tumor formation in vivo. Taken together, our data suggest that targeted therapy against AXL, in combination with systemic therapies, has the potential to improve response to anticancer therapies and to reduce breast cancer recurrence and metastases.

Indexed as

Epithelial-Mesenchymal TransitionAnimalsAntineoplastic AgentsAxl Receptor Tyrosine KinaseBreast NeoplasmsCarcinogenesisCell Line, TumorCell MovementCell ProliferationDrug Resistance, NeoplasmFemaleHumansMiceMice, TransgenicMolecular Targeted TherapyNeoplasm TransplantationamuvatinibAntineoplastic AgentsAxl Receptor Tyrosine KinaseNF-kappa BPiperazinesProto-Oncogene ProteinsPyrimidinesReceptor Protein-Tyrosine KinasesThiourea

Identifiers

PMID23474758
PMCPMC3994701
OpenAlexW2149542744

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.