Related Experiment Video

Updated: Mar 7, 2026

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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Usp9x regulates Ets-1 ubiquitination and stability to control NRAS expression and tumorigenicity in melanoma

Harish Potu1, Luke F Peterson1, Malathi Kandarpa1

  • 1Department of Internal Medicine/Division of Hematology/Oncology, University of Michigan School of Medicine and Comprehensive Cancer Center, Ann Arbor, Michigan 48109, USA.

Nature Communications
|February 16, 2017
PubMed

Insights

The deubiquitinating enzyme Usp9x stabilizes Ets-1, promoting melanoma tumor growth. Inhibiting Usp9x or combining it with MEK inhibitors suppressed melanoma progression, offering a potential new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • ETS transcription factors are crucial for tumorigenicity and often deregulated in cancer.
  • Targeting ETS proteins presents a potential therapeutic avenue for cancer treatment.

Purpose of the Study:

  • To investigate the role of the deubiquitinating enzyme Usp9x in regulating Ets-1 stability and its impact on metastatic melanoma.
  • To explore the therapeutic potential of targeting the Usp9x-Ets-1 axis in melanoma.

Main Methods:

  • Assessed Ets-1 deubiquitination and proteasomal degradation regulated by Usp9x.
  • Examined Usp9x and Ets-1 expression levels in melanoma tissues.
  • Investigated the effect of Usp9x inhibition and combination therapy with MEK inhibitors on melanoma growth.

Main Results:

  • Usp9x deubiquitinates Ets-1, preventing its proteasomal degradation and enhancing melanoma tumorigenicity.
  • Elevated Usp9x and Ets-1 levels correlate with melanoma metastasis.
  • Therapeutic inhibition of Usp9x, alone or in combination with MEK inhibitors, significantly suppressed melanoma growth.

Conclusions:

  • Usp9x plays a critical role in modulating the Ets-1/NRAS regulatory network in melanoma.
  • Targeting Usp9x represents a promising therapeutic strategy for metastatic melanoma.

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