The tumor suppressor BAP1 cooperates with BRAFV600E to promote tumor formation in cutaneous melanoma.

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.

authors

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,Dixit

doi

10.1111/pcmr.12735

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

269-279

issue

2

eissn

1755-1471

issn

1755-148X

journal_volume

32

pub_type

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