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Updated: Nov 24, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
BAP1 deletion abrogates growth and metastasis of murine cutaneous melanoma
Abstract:
Although germline mutations in BRCA-associated protein-1 (BAP1) predispose to cutaneous melanoma (CM), BAP1 is rarely mutated in primary CM outside the familial context. The role of BAP1 in the pathogenesis of CM remains obscure. Here, we discovered an unexpected role of BAP1 in suppressing CM growth and metastasis. BAP1 deletion by CRISPR-Cas9 system severely compromises colony-forming capability of murine CM cell line B16-F10 and human CM cell lines, SK-MEL-28 and A375. Furthermore, BAP1 loss abrogates tumor growth and lung metastasis in murine syngeneic tumor models. Deletion of BAP1 in B16-F10 cells leads to preferential downregulation of genes accompanied with increased H2A ubiquitination at lysine 119. Transcriptomic characterization of BAP1 deletion reveals multiple deregulated cellular functions including extracellular matrix-receptor interaction and MAPK signaling pathway which may contribute to BAP1's effect on metastasis and proliferation. Our findings indicate that BAP1 could be a potential therapeutic target for CM.
Insights
BRCA-associated protein-1 (BAP1) unexpectedly suppresses cutaneous melanoma (CM) growth and metastasis. Loss of BAP1 impairs tumor formation and spread, suggesting BAP1 as a potential therapeutic target for CM.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Germline mutations in BRCA-associated protein-1 (BAP1) are linked to hereditary cutaneous melanoma (CM).
- The specific role of BAP1 in the development of primary CM, particularly in non-familial cases, is not well understood.
Purpose of the Study:
- To investigate the function of BAP1 in the pathogenesis of cutaneous melanoma.
- To determine if BAP1 plays a role in suppressing CM growth and metastasis.
Main Methods:
- CRISPR-Cas9 gene editing was used to delete BAP1 in murine (B16-F10) and human (SK-MEL-28, A375) CM cell lines.
- Tumor growth and lung metastasis were assessed in murine syngeneic models following BAP1 deletion.
- Transcriptomic analysis and H2A ubiquitination assays were performed to understand the molecular mechanisms.
Main Results:
- BAP1 deletion significantly reduced the colony-forming ability of CM cell lines.
- Loss of BAP1 abrogated tumor growth and lung metastasis in vivo.
- BAP1 deletion led to downregulation of specific genes, increased H2A ubiquitination at lysine 119, and deregulation of pathways like extracellular matrix-receptor interaction and MAPK signaling.
Conclusions:
- BAP1 acts as a suppressor of cutaneous melanoma growth and metastasis.
- The findings highlight BAP1 as a potential therapeutic target for CM treatment.
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