Investigating the role of LSD2 as an epigenetic regulator in Ewing sarcoma.

Investigating the role of LSD2 as an epigenetic regulator in Ewing sarcoma. Oncotarget. 2019 Jun 11;10(39):3865-3878 Authors: Patel PO, Pishas KI, Taslim C, Selich-Anderson J, Theisen ER, Lessnick SL Abstract Ewing sarcoma is the second most common solid bone malignancy diagnosed in pediatric and young adolescent populations. Despite aggressive multi-modal treatment strategies, 5-year event-free survival remains at 75% for patients with localized disease and 20% for patients with metastases. Thus, the need for novel therapeutic options is imperative. Recent studies have focused on epigenetic misregulation in Ewing sarcoma development and potential new oncotargets for treatment. This project focused on the study of LSD2, a flavin-dependent histone demethylase found to be overexpressed in numerous cancers. We previously demonstrated that Ewing sarcoma cell lines are extremely susceptible to small molecule LSD1 blockade with SP-2509. Drug sensitivity correlated with the degree of LSD2 induction following treatment. As such, the purpose of this study was to determine the role of LSD2 in the epigenetic regulation of Ewing sarcoma, characterize genes regulated by LSD2, and examine the impact of SP-2509 drug treatment on LSD2 gene regulation. Genetic depletion (shRNA) of LSD2 significantly impaired oncogenic transformation with only a modest impact on proliferation. Transcriptional analysis of Ewing sarcoma cells following LSD2knockdown rev...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research