| First Author | Yu Y | Year | 2018 |
| Journal | Cancer Cell | Volume | 33 |
| Issue | 2 | Pages | 322-336.e8 |
| PubMed ID | 29438700 | Mgi Jnum | J:257785 |
| Mgi Id | MGI:6119352 | Doi | 10.1016/j.ccell.2018.01.002 |
| Citation | Yu Y, et al. (2018) Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma. Cancer Cell 33(2):322-336.e8 |
| abstractText | 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. |
