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The tumor suppressor BAP 1 cooperates with BRAFV 600E to promote tumor formation in cutaneous melanoma
Author(s) -
Webster Joshua D.,
Pham Trang H.,
Wu Xiumin,
Hughes Nicolas W.,
Li Zhongwu,
Totpal Klara,
Lee HoJune,
Calses Philamer C.,
Chaurushiya Mira S.,
Stawiski Eric W.,
Modrusan Zora,
Chang Matthew T.,
Tran Christopher,
Lee Wyne P.,
Chalasani Sreedevi,
Hung Jeffrey,
Sharma Neeraj,
Chan Sara,
Hotzel Kathy,
Talevich Eric,
Shain Alan,
Xu Mengshu,
Lill Jennie,
Dixit Vishva M.,
Bastian Boris C.,
Dey Anwesha
Publication year - 2019
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12735
Subject(s) - bap1 , melanoma , cancer research , suppressor , deubiquitinating enzyme , cancer , biology , null cell , ubiquitin , cell culture , gene , genetics
The deubiquitinating enzyme BAP 1 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 (BRAF V600E ) 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, BAP 1 functions as a tumor suppressor and limits tumor progression in melanoma.