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Updated: Dec 18, 2025
06:09
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
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Heme oxygenase promotes B-Raf-dependent melanosphere formation
Kimberly J Jasmer1,2, Jie Hou3, Philip Mannino2,4
1Division of Biological Sciences, University of Missouri, Columbia, Missouri, USA.
Pigment Cell & Melanoma Research
|June 20, 2020
Summary
Heme oxygenase activity promotes melanoma stem cell formation. Inhibiting heme oxygenase 1 (HMOX1) or heme oxygenase 2 (HMOX2) reduces melanoma stemness, highlighting their role in tumor growth.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Heme is crucial for metabolism; its degradation by heme oxygenases (HMOX1/2) yields carbon monoxide, iron, and biliverdin.
- HMOX1 expression is regulated by NFE2L2 and Bach1, and its induction correlates with tumor growth and therapy resistance.
- Elevated NFE2L2 is common in tumor cells, promoting the expression of NFE2L2-dependent genes.
Purpose of the Study:
- To investigate the role of heme oxygenase activity in melanosphere formation in human melanoma cells.
- To determine the impact of HMOX1 and HMOX2 regulation on melanoma stem cell characteristics.
Main Methods:
- Investigated melanosphere formation in human melanoma cell lines.
- Utilized genetic ablation of HMOX1 and pharmacological inhibition of heme oxygenase activity (tin protoporphyrin).
- Performed global transcriptome analyses to identify associated molecular pathways.
Main Results:
- Transcriptional induction of HMOX1 or HMOX2 significantly increased melanosphere formation.
- Genetic deletion of HMOX1 reduced melanosphere formation.
- Inhibition of heme oxygenase activity suppressed melanosphere formation driven by Bach1 derepression or B-RafV600E.
- Transcriptome analysis revealed involvement of focal adhesion and extracellular matrix genes.
Conclusions:
- Heme oxygenase activity plays a novel and critical role in promoting melanoma stem cell formation.
- Targeting heme oxygenase activity represents a potential therapeutic strategy to inhibit melanoma stemness and progression.
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