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Histone methyltransferase SETDB1 contributes to melanoma tumorigenesis and serves as a new potential therapeutic target
Author(s) -
Orouji Elias,
Federico Aniello,
Larribère Lionel,
Novak Daniel,
Lipka Daniel B.,
Assenov Yassen,
Sachindra Sachindra,
Hüser Laura,
Granados Karol,
Gebhardt Christoffer,
Plass Christoph,
Umansky Viktor,
Utikal Jochen
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32432
Subject(s) - histone methyltransferase , carcinogenesis , cancer research , methyltransferase , histone , melanoma , ezh2 , biology , histone h3 , epigenetics , microbiology and biotechnology , cancer , genetics , methylation , gene
Alterations in histone modifications play a crucial role in the progression of various types of cancer. The histone methyltransferase SETDB1 catalyzes the addition of methyl groups to histone H3 at lysine 9. Here, we describe how overexpression of SETDB1 contributes to melanoma tumorigenesis. SETDB1 is highly amplified in melanoma cells and in the patient tumors. Increased expression of SETDB1 , which correlates with SETDB1 amplification, is associated with a more aggressive phenotype in in vitro and in vivo studies. Mechanistically, SETDB1 implements its effects via regulation of thrombospondin 1, and the SET‐domain of SETDB1 is essential for the maintenance of its tumorigenic activity. Inhibition of SETDB1 reduces cell growth in melanomas resistant to targeted treatments. Our results indicate that SETDB1 is a major driver of melanoma development and may serve as a potential future target for the treatment of this disease.