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Updated: Sep 13, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

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

Published on: June 7, 2019

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PTRF Confers Melanoma-Acquired Drug Resistance Through the Upregulation of EGFR

Miao Wang1, Ying Cao1, Chengcheng Ren1

  • 1Zhejiang Key Laboratory of Medical Epigenetics, Zhejiang Key Laboratory of Aging and Cancer Biology, Hangzhou Normal University School of Basic Medical Sciences, Hangzhou, China.

Cell Proliferation
|August 1, 2025
PubMed

Insights

PTRF upregulation increases caveolae in melanoma, driving resistance to BRAF and MEK inhibitors. Targeting PTRF may overcome drug resistance by downregulating EGFR and restoring sensitivity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Melanoma is a serious skin cancer often driven by BRAF mutations.
  • Targeted therapies like BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are effective but face inevitable resistance.
  • Mechanisms of acquired resistance to melanoma targeted therapies are not fully understood.

Purpose of the Study:

  • To investigate the role of PTRF and caveolae in melanoma drug resistance.
  • To elucidate the molecular mechanisms by which PTRF contributes to resistance against BRAFi and MEKi therapies.

Main Methods:

  • Analysis of PTRF and caveolae in drug-resistant melanoma cell lines and patient tissues.
  • Gene knockdown and ectopic expression of PTRF in melanoma cells.
  • Assessment of cell proliferation, apoptosis, and drug sensitivity.
  • Evaluation of EGFR expression in relation to PTRF and drug resistance.

Main Results:

  • Increased caveolae number and PTRF expression in drug-resistant melanoma cells and tissues.
  • PTRF knockdown reduced proliferation and increased apoptosis in resistant cells.
  • Ectopic PTRF expression conferred BRAFi/MEKi resistance to parental cells.
  • PTRF upregulation correlated with increased EGFR expression, a key driver of resistance.

Conclusions:

  • PTRF is a critical mediator of resistance to BRAFi and MEKi therapies in melanoma.
  • PTRF promotes drug resistance, at least partly, by upregulating EGFR expression.
  • Targeting PTRF may represent a novel therapeutic strategy to overcome melanoma targeted therapy resistance.
Keywords:
EGFRPTRFcaveolaedrug resistancemelanoma

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