Yu, Yong, Schleich, Kolja, Yue, Bin, Ji, Sujuan, Lohneis, Philipp, Kemper, Kristel, Silvis, Mark S., Qutob, Nouar, van Rooijen, Ellen, Werner-Klein, Melanie, Li, Lianjie, Dhawan, Dhriti, Meierjohann, Svenja, Reimann, Maurice, Elkahloun, Abdel, Treitschke, Steffi, Doerken, Bernd, Speck, Christian, Mallette, Frederick A. ORCID: 0000-0001-7932-0338, Zon, Leonard I., Holmen, Sheri L., Peeper, Daniel S., Samuels, Yardena ORCID: 0000-0002-3349-7266, Schmitt, Clemens A. ORCID: 0000-0002-4731-2226 and Lee, Soyoung ORCID: 0000-0002-4614-2931 (2018). Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma. Cancer Cell, 33 (2). S. 322 - 345. CAMBRIDGE: CELL PRESS. ISSN 1878-3686

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Abstract

Oncogene-induced senescence, e.g., in melanocytic nevi, terminates the expansion of pre-malignant cells via transcriptional silencing of proliferation-related genes due to decoration of their promoters with repressive trimethylated histone H3 lysine 9 (H3K9) marks. We show here that structurally distinct H3K9-active demethylases-the lysine-specific demethylase-1 (LSD1) and several Jumonji C domain-containing moieties (such as JMJD2C)-disable senescence and permit Ras/Braf-evoked transformation. In mouse and zebrafish models, enforced LSD1 or JMJD2C expression promoted Braf-V600E-driven melanomagenesis. A large subset of established melanoma cell lines and primary human melanoma samples presented with a collective upregulation of related and unrelated H3K9 demethylase activities, whose targeted inhibition restored senescence, even in Braf inhibitor-resistant melanomas, evoked secondary immune effects and controlled tumor growth in vivo.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Yu, YongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schleich, KoljaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yue, BinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ji, SujuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lohneis, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kemper, KristelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Silvis, Mark S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Qutob, NouarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Rooijen, EllenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Werner-Klein, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, LianjieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dhawan, DhritiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meierjohann, SvenjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reimann, MauriceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elkahloun, AbdelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Treitschke, SteffiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doerken, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speck, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mallette, Frederick A.UNSPECIFIEDorcid.org/0000-0001-7932-0338UNSPECIFIED
Zon, Leonard I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holmen, Sheri L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peeper, Daniel S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Samuels, YardenaUNSPECIFIEDorcid.org/0000-0002-3349-7266UNSPECIFIED
Schmitt, Clemens A.UNSPECIFIEDorcid.org/0000-0002-4731-2226UNSPECIFIED
Lee, SoyoungUNSPECIFIEDorcid.org/0000-0002-4614-2931UNSPECIFIED
URN: urn:nbn:de:hbz:38-196028
DOI: 10.1016/j.ccell.2018.01.002
Journal or Publication Title: Cancer Cell
Volume: 33
Number: 2
Page Range: S. 322 - 345
Date: 2018
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1878-3686
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ONCOGENE-INDUCED SENESCENCE; CELLULAR SENESCENCE; HISTONE; CANCER; LSD1; P53; HETEROCHROMATIN; LYMPHOMAGENESIS; METHYLATION; ACTIVATIONMultiple languages
Oncology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/19602

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