ArticleCell communication and signaling : CCS2019
Heme oxygenase 1 facilitates cell proliferation via the B-Raf-ERK signaling pathway in melanoma.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Heme oxygenase-1 in thyroid cancer: a context-dependent regulator.Journal of endocrinological investigation · 2026Review
- Apoptosis Induction and MAPK Pathway Modulation by Lagerstroemia floribunda in Melanoma: Experimental and Computational Insights.Applied biochemistry and biotechnology · 2026Article
- Mapping of the hSOX10 protein interactome in human melanoma.bioRxiv : the preprint server for biology · 2025Article
- Redox pathways in melanoma.Advances in cancer research · 2024Review
- Hyperforin Enhances Heme Oxygenase-1 Expression Triggering Lipid Peroxidation in BRAF-Mutated Melanoma Cells and Hampers the Expression of Pro-Metastatic Markers.Antioxidants (Basel, Switzerland) · 2023Article
- Heme Oxygenase-1 Overexpression Promotes Uveal Melanoma Progression and Is Associated with Poor Clinical Outcomes.Antioxidants (Basel, Switzerland) · 2022Article
- Heme oxygenase 1 overexpression induces immune evasion of acute myeloid leukemia against natural killer cells by inhibiting CD48.Journal of translational medicine · 2022Article
- Non-canonical vs. Canonical Functions of Heme Oxygenase-1 in Cancer.Journal of cancer prevention · 2022Review
- Heme Oxygenase-1 Has a Greater Effect on Melanoma Stem Cell Properties Than the Expression of Melanoma-Initiating Cell Markers.International journal of molecular sciences · 2022Article
- Review
- Nuclear Localization of BRAFCancers · 2022Article
- The non-canonical effects of heme oxygenase-1, a classical fighter against oxidative stress.Redox biology · 2021Review
- Clinical Significance of Heme Oxygenase 1 in Tumor Progression.Antioxidants (Basel, Switzerland) · 2021Review
- 15-Deoxy-ΔCells · 2021Article
- Heme oxygenase 1: a novel oncogene in multiple gynecological cancers.International journal of biological sciences · 2021Review
- Heme oxygenase promotes B-Raf-dependent melanosphere formation.Pigment cell & melanoma research · 2020Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite therapeutic advancements (e.g. B-RAF inhibitors) targeting cutaneous melanoma, many cellular processes, including inducible heme oxygenase 1 (HO-1), counteract treatments for malignancies. So there is an urgent need to find biological treatment targets, develop new therapeutic approaches and achieve longer responses. This study aimed to explore the relationship of HO-1 and B-Raf via mediating ERK1/2 signaling on cell cycle in melanoma.
methodsImmunohistochemistry was applied to evaluate the levels of HO-1 and B-Raf expression in melanoma tissues and adjacent healthy tissues. Co-immunoprecipitation (Co-IP) assessed the interaction of HO-1 with B-Raf. Further study overexpression and knock-down of HO-1 in A375 cell lines, especially knockout HO-1 using CRISPR-Cas9, verified HO-1 regulate cell proliferation in vivo and in vitro. Finally, Western blot analysis and qRT-PCR were performed to investigate the mechanisms by which HO-1 mediates cell cycle by B-RAF-ERK1/2 signaling.
resultsFirst, histology and Co-IP show that HO-1 interacts with B-Raf directly in melanoma tissue. Further study illustrated that HO-1 overexpression promotes melanoma cell proliferation while HO-1 reduction represses melanoma cell proliferation because of HO-1 affects cell cycle. Mechanistic studies revealed that HO-1 was associated with a marked activation of B-RAF-ERK1/2 signaling and led to CDK2/cyclin E activation, thereby promoting melanoma proliferation.
conclusionsOur result reveals a previously unknown mechanism that the HO-1-B-RAF-ERK axis plays an important role in melanoma cell proliferation. Therapeutic target on HO-1 could be a novel method for treating melanoma.
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