Related Experiment Video
Updated: Jul 1, 2025
06:09
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
8.7K
p300 KAT regulates SOX10 stability and function in human melanoma.
Aaron Waddell1, Nicole Grbic1, Kassidy Leibowitz1
1Department of Dermatology, Boston University Aram V. Chobanian & Edward Avedisian School of Medicine, 609 Albany Street, Boston, MA, USA 02118.
Biorxiv : the Preprint Server for Biology
|March 12, 2024
Summary
Targeting SOX10 in melanoma is challenging due to therapy resistance. Inhibiting EP300 (a lysine acetyltransferase) with A-485 stabilizes SOX10, reducing melanoma growth and invasion.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- SOX10 is crucial for melanoma growth but its loss promotes invasive phenotypes.
- Therapeutic strategies must balance inhibiting proliferation and preventing invasion.
Approach:
- Investigated co-amplification of EP300 and SOX10 in melanomas.
- Examined p300 lysine acetyltransferase (KAT) activity's role in SOX10 stability.
- Utilized the p300 inhibitor A-485 to modulate SOX10 levels and melanoma cell behavior.
Key Points:
- EP300 and SOX10 genes are frequently co-amplified in various melanoma types.
- p300 KAT activity stabilizes SOX10 protein; A-485 induces SOX10 degradation.
- A-485 inhibits proliferation in SOX10+ melanoma cells.
- A-485 reduces invasion in AXLhigh/MITFlow melanoma cells by downregulating metastasis genes.
Conclusions:
- The SOX10/p300 axis is vital for melanoma growth and invasion.
- p300 inhibition via A-485 presents a potential therapeutic strategy for SOX10-dependent melanomas.
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