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.
journal_name
Pigment Cell Melanoma Resjournal_title
Pigment cell & melanoma researchauthors
Webster JD,Pham TH,Wu X,Hughes NW,Li Z,Totpal K,Lee HJ,Calses PC,Chaurushiya MS,Stawiski EW,Modrusan Z,Chang MT,Tran C,Lee WP,Chalasani S,Hung J,Sharma N,Chan S,Hotzel K,Talevich E,Shain A,Xu M,Lill J,Dixitdoi
10.1111/pcmr.12735subject
Has Abstractpub_date
2019-03-01 00:00:00pages
269-279issue
2eissn
1755-1471issn
1755-148Xjournal_volume
32pub_type
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