The tumor suppressor BAP1 cooperates with BRAFV600E to promote tumor formation in cutaneous melanoma.
Pigment Cell Melanoma Res
; 32(2): 269-279, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30156010
ABSTRACT
The deubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with a high risk of mesothelioma and melanocytic tumors. Here, we show that Bap1 deletion in melanocytes cooperates with the constitutively active, oncogenic form of BRAF (BRAFV600E ) and UV to cause melanoma in mice, albeit at very low frequency. In addition, Bap1-null melanoma cells derived from mouse tumors are more aggressive and colonize and grow at distant sites more than their wild-type counterparts. Molecularly, Bap1-null melanoma cell lines have increased DNA damage measured by γH2aX and hyperubiquitination of histone H2a. Therapeutically, these Bap1-null tumors are completely responsive to BRAF- and MEK-targeted therapies. Therefore, BAP1 functions as a tumor suppressor and limits tumor progression in melanoma.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
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Proteínas Supresoras de Tumor
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Ubiquitina Tiolesterasa
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Proteínas Proto-Oncogénicas B-raf
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Carcinogénesis
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Melanoma
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Mutación
Límite:
Animals
Idioma:
En
Revista:
Pigment Cell Melanoma Res
Asunto de la revista:
NEOPLASIAS
Año:
2019
Tipo del documento:
Article