Related Experiment Video

Updated: Aug 30, 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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Suppression of Ca2+ signaling enhances melanoma progression

Scott Gross1, Robert Hooper1, Dhanendra Tomar2

  • 1Fels Cancer Institute for Personalized Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.

The EMBO Journal
|August 30, 2022
PubMed

Insights

Store-operated Ca2+ entry (SOCE) suppression promotes melanoma metastasis by altering gene expression and metabolism. Inhibiting cholesterol biosynthesis or enhancing SOCE can reverse invasiveness in human melanoma.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • The role of store-operated Ca2+ entry (SOCE) in melanoma metastasis is debated.
  • Understanding the mechanisms regulating melanoma progression is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of UV-induced SOCE in melanoma metastasis.
  • To elucidate the molecular mechanisms linking SOCE, cholesterol biosynthesis, and melanoma progression.

Main Methods:

  • UV irradiation of melanoma cells
  • Assessment of metastasis
  • Analysis of cholesterol biosynthesis pathways
  • Gene expression profiling
  • Metabolic analyses
  • Examination of human melanoma explants

Main Results:

  • UV-induced SOCE suppression is critical for melanoma metastasis.
  • UV-induced cholesterol biosynthesis drives SOCE suppression and metastasis.
  • SOCE suppression alters gene expression, increasing invasion and reducing glucose metabolism.
  • Human melanoma explants show reduced SOCE dependent on cholesterol biosynthesis.
  • Invasiveness is reversible with cholesterol biosynthesis inhibitors or SOCE potentiation.

Conclusions:

  • Contrary to current understanding, Ca2+ signals can inhibit melanoma invasion.
  • Suppression of SOCE promotes melanoma invasion and metastasis.
  • Targeting cholesterol biosynthesis or enhancing SOCE may offer therapeutic strategies for melanoma.
Keywords:
Orai1STIM1calciummelanomametastasis

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