Yu, Yong and Schleich, Kolja and Yue, Bin and Ji, Sujuan and Lohneis, Philipp and Kemper, Kristel and Silvis, Mark S. and Qutob, Nouar and van Rooijen, Ellen and Werner-Klein, Melanie and Li, Lianjie and Dhawan, Dhriti and Meierjohann, Svenja and Reimann, Maurice and Elkahloun, Abdel and Treitschke, Steffi and Doerken, Bernd and Speck, Christian and Mallette, Frederick A. and Zon, Leonard I. and Holmen, Sheri L. and Peeper, Daniel S. and Samuels, Yardena and Schmitt, Clemens A. and Lee, Soyoung (2018) Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma. CANCER CELL, 33 (2). 322-+. ISSN 1535-6108, 1878-3686
Full text not available from this repository. (Request a copy)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: | Article |
|---|---|
| Uncontrolled Keywords: | ONCOGENE-INDUCED SENESCENCE; CELLULAR SENESCENCE; HISTONE; CANCER; LSD1; P53; HETEROCHROMATIN; LYMPHOMAGENESIS; METHYLATION; ACTIVATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Mar 2020 09:54 |
| Last Modified: | 18 Mar 2020 09:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15049 |
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