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Updated: Jan 8, 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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A BRN2:MYC transcriptional axis regulates interconversion between therapy-resistant and tumorigenic phenotypes in

Yuntian Zhang1, Marcus A Urquijo2, Rebecca G Zitnay3

  • 1Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.

Cell Reports
|December 17, 2025
PubMed

Insights

Melanoma cells exhibit accelerated switching between transcriptional states, unlike melanocytes. This rapid phenotypic switching, driven by MYC and BRN2, is key to melanoma progression and therapy resistance.

Area of Science:

  • Oncology
  • Cell Biology
  • Cancer Research

Background:

  • Metastatic spread and therapeutic resistance are primary drivers of cancer mortality.
  • Melanoma progression involves transitions between distinct cellular transcriptional states.
  • Understanding melanoma cell state switching mechanisms is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the mechanisms of transcriptional state switching in melanoma cells.
  • To compare melanoma cell state switching with that of melanocytes.
  • To identify distinct melanoma cell phenotypes and their roles in tumor initiation and resistance.

Main Methods:

  • Isolation and characterization of distinct melanoma cell states.
  • Phenotypic and transcriptional profiling of melanoma and melanocyte states.
  • Analysis of transition frequencies between cellular states.

Main Results:

  • Identified a MYC-driven state essential for tumor initiation and sensitive to BRAF inhibition.
  • Identified a dedifferentiated, BRN2-high state associated with therapy resistance.
  • Discovered that BRN2-high states exist in both melanoma and melanocytes, while MYC states are melanoma-exclusive.
  • Observed an increased frequency of state transitions in melanoma cells compared to melanocytes.

Conclusions:

  • Accelerated phenotypic switching, not just state diversity, defines melanoma progression.
  • Targeting rapid state transitions may offer novel therapeutic strategies for melanoma.
  • Distinct transcriptional states, like MYC-driven and BRN2-high, play critical roles in melanoma's aggressive behavior.
Keywords:
BRN2CP: CancerMITFMYCmelanocytesmelanomaoncogenic competencephenotype switchingplasticityquantitative phase imagingsingle-cell sequencing

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