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Updated: Mar 22, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

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The transcription factor RUNX2 regulates receptor tyrosine kinase expression in melanoma

Rajeev K Boregowda1, Daniel J Medina1, Elke Markert2

  • 1Division of Medical Oncology, Department of Medicine, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.

Oncotarget
|April 23, 2016
PubMed

Insights

The transcription factor RUNX2 drives receptor tyrosine kinase (RTK)-based autocrine loops in melanoma. RUNX2 also mediates resistance to BRAF V600E inhibitors by upregulating RTKs, suggesting it

Area of Science:

  • Melanoma research
  • Cancer biology
  • Molecular mechanisms in cancer

Background:

  • Receptor tyrosine kinase (RTK)-based autocrine loops activate MAPK and PI3K/AKT pathways in melanoma.
  • The molecular mechanisms generating these autocrine loops remain largely unknown.

Purpose of the Study:

  • To investigate the role of the transcription factor RUNX2 in regulating RTK expression in melanoma.
  • To explore RUNX2's involvement in melanoma cell signaling and drug resistance.

Main Methods:

  • Assessed RTK expression in RUNX2-deficient melanoma cells.
  • Examined RUNX2 and RTK co-expression in melanoma cells and patient samples.
  • Analyzed downstream signaling pathway activation (AKT) following RUNX2 knockdown.
  • Investigated RUNX2 and RTK expression in melanoma cells resistant to BRAF V600E inhibitors.

Main Results:

  • RUNX2 deficiency led to decreased expression of EGFR, IGF-1R, and PDGFRβ.
  • Co-expression of RUNX2 and AXL was observed in melanoma cells and patient samples.
  • RUNX2 knockdown reduced phosphoAKT2 and phosphoAKT levels.
  • Melanoma cells resistant to BRAF V600E inhibitor PLX4720 showed increased RUNX2, EGFR, IGF-1R, and AXL expression.

Conclusions:

  • RUNX2 plays a significant role in regulating RTK expression in melanoma.
  • RUNX2 is implicated in RTK-based autocrine loops and melanoma cell signaling.
  • RUNX2 may mediate resistance to BRAF V600E inhibitors through RTK upregulation.
Keywords:
RUNX2melanomareceptor tyrosine kinaseresistance to targeted therapytranscription factor

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