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Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma
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Ubiquitination and adaptive responses to BRAF inhibitors in Melanoma

Azad Saei1,2, Pieter Johan Adam Eichhorn3,4,5

  • 1Genome Institute of Singapore, ASTAR, Singapore.

Molecular & Cellular Oncology
|September 29, 2018
PubMed

Insights

The USP28/FBW7 complex normally degrades BRAF, inhibiting the MAPK pathway. Loss of this function in BRAF mutant melanoma causes resistance to targeted therapies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Targeted therapy response is often limited by feedback loops.
  • Melanoma harbors frequent BRAF mutations, leading to MAPK pathway activation.

Purpose of the Study:

  • To investigate the role of the USP28/FBW7 complex in regulating the MAPK pathway.
  • To understand the mechanism of resistance to BRAF inhibitor therapies in melanoma.

Main Methods:

  • Investigated the interaction and function of USP28/FBW7 complex.
  • Analyzed BRAF protein degradation and MAPK pathway activity.
  • Studied melanoma patient samples with BRAF mutations.

Main Results:

  • The USP28/FBW7 complex acts as a negative regulator of the MAPK pathway.
  • This complex targets BRAF for degradation.
  • This degradation mechanism is impaired in many BRAF-mutant melanoma patients.

Conclusions:

  • USP28/FBW7-mediated BRAF degradation is crucial for controlling MAPK signaling.
  • Loss of this negative feedback loop contributes to BRAF inhibitor resistance in melanoma.
Keywords:
USP28/BRAF/Melanoma/Vemurafenib resistance

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