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Updated: Oct 25, 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

9.1K

The AMP-dependent kinase pathway is upregulated in BAP1 mutant uveal melanoma

Vivian Chua1, Anna Han1, Nelisa Bechtel1

  • 1Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.

Pigment Cell & Melanoma Research
|August 4, 2021
PubMed

Insights

Metastatic uveal melanoma (UM) with BAP1 mutations shows elevated AMP-dependent kinase (AMPK) pathway activity. Inhibiting AMPK may offer a new therapeutic strategy for this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Metastatic uveal melanoma (UM) exhibits resistance to current therapies.
  • Loss-of-function mutations in BRCA1-associated protein 1 (BAP1) are implicated in UM progression.
  • Identifying novel therapeutic targets for metastatic UM is critical.

Purpose of the Study:

  • To investigate the role of the AMP-dependent kinase (AMPK) pathway in BAP1-mutated UM.
  • To explore the therapeutic potential of targeting the AMPK pathway in metastatic UM.

Main Methods:

  • Analysis of AMPK and acetyl-CoA-carboxylase (ACC) phosphorylation levels in UM tumors with and without BAP1 alterations.
  • BAP1 re-expression experiments in BAP1-null UM cell lines.
  • Knockdown of AMPKα1/2 to assess its effect on cell viability.
  • Investigation of upstream kinases (CaMKK2, LKB1) involved in AMPK phosphorylation.

Main Results:

  • Elevated phosphorylation of AMPK and its downstream effector ACC was observed in BAP1-mutant UM tumors compared to wild-type.
  • Re-expression of BAP1 reduced pAMPK and pACC levels in UM cell lines.
  • AMPK phosphorylation is potentially mediated by CaMKK2 and LKB1 in BAP1 mutant UM.
  • Knockdown of AMPKα1/2 significantly reduced the viability of BAP1 mutant UM cells.

Conclusions:

  • The AMPK pathway plays a crucial role in the survival of BAP1-mutant UM.
  • Targeting the AMPK pathway represents a promising novel therapeutic strategy for metastatic UM.
Keywords:
AMPKBAP1stressuveal melanoma

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