Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours, Nature, vol.359, issue.6391, pp.162-167, 1992. ,
A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nature genetics, vol.6, pp.146-51, 1994. ,
Structure-function based molecular relationships in Ewing's sarcoma. BioMed research international, p.798426, 2015. ,
Longitudinal follow-up of adult survivors of Ewing sarcoma: A report from the Childhood Cancer Survivor Study, 2017. ,
The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation, PLoS genetics, vol.10, issue.7, p.1004475, 2014. ,
The genomic landscape of pediatric Ewing sarcoma, Cancer discovery, vol.4, issue.11, pp.1326-1367, 2014. ,
Mutational heterogeneity in cancer and the search for new cancer-associated genes, Nature, vol.499, issue.7457, pp.214-222, 2013. ,
Epigenetic mechanisms and genome stability, Clinical epigenetics, vol.2, issue.2, pp.299-314, 2011. ,
Histone demethylation mediated by the nuclear amine oxidase homolog LSD1, Cell, vol.119, issue.7, pp.941-53, 2004. ,
Therapeutic opportunities in Ewing sarcoma: EWS-FLI inhibition via LSD1 targeting, Oncotarget, vol.7, issue.14, pp.17616-17646, 2016. ,
Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer, PloS one, vol.7, issue.4, p.35065, 2012. ,
Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer research, vol.69, pp.2065-71, 2009. ,
High expression of lysine-specific demethylase 1 correlates with poor prognosis of patients with esophageal squamous cell carcinoma. Biochemical and biophysical research communications, vol.437, pp.192-200, 2013. ,
Expression of Lysine-specific demethylase 1 in human epithelial ovarian cancer, Journal of ovarian research, vol.8, p.28, 2015. ,
Lysine-specific demethylase 1 (LSD1/ KDM1A/AOF2/BHC110) is expressed and is an epigenetic drug target in chondrosarcoma, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Human pathology, vol.43, pp.1300-1307, 2012. ,
High-throughput virtual screening identifies novel N'-(1-phenylethylidene)-benzohydrazides as potent, specific, and reversible LSD1 inhibitors, Journal of medicinal chemistry, vol.56, issue.23, pp.9496-508, 2013. ,
Reversible LSD1 inhibition interferes with global EWS/ETS transcriptional activity and impedes Ewing sarcoma tumor growth. Clinical cancer research : an official journal of the American Association for Cancer Research, vol.20, pp.4584-97, 2014. ,
A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC, Cancer cell, vol.28, issue.1, pp.57-69, 2015. ,
Assays for detecting the unfolded protein response, Methods in enzymology, vol.490, pp.31-51, 2011. ,
Gene Expression Profiling of Ewing Sarcoma Tumors Reveals the Prognostic Importance of Tumor-Stromal Interactions: A Report from the Children's Oncology Group. The journal of pathology Clinical research, vol.1, pp.83-94, 2015. ,
Microarray analysis of Ewing's sarcoma family of tumours reveals characteristic gene expression signatures associated with metastasis and resistance to chemotherapy, Eur J Cancer, vol.44, issue.5, pp.699-709, 2008. ,
Prediction of high risk Ewing's sarcoma by gene expression profiling, Oncogene, vol.23, issue.55, pp.8997-9006, 2004. ,
Array CGH and geneexpression profiling reveals distinct genomic instability patterns associated with DNA repair and cell-cycle checkpoint pathways in Ewing's sarcoma, Oncogene, vol.27, issue.14, pp.2084-90, 2008. ,
Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma, Nature genetics, vol.44, issue.3, pp.323-330, 2012. ,
URL : https://hal.archives-ouvertes.fr/inserm-02438686
Reversible lysine-specific demethylase 1 antagonist HCI-2509 inhibits growth and decreases c-MYC in castration-and docetaxel-resistant prostate cancer cells. Prostate cancer and prostatic diseases, vol.19, pp.349-57, 2016. ,
Reversible LSD1 inhibition with HCI-2509 induces the p53 gene expression signature and disrupts the MYCN signature in high-risk neuroblastoma cells, Oncotarget, vol.9, issue.11, pp.9907-9931, 2018. ,
Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations, Cancer discovery, vol.4, issue.11, pp.1342-53, 2014. ,
Characterization and drug resistance patterns of Ewing's sarcoma family tumor cell lines, PloS one, vol.8, issue.12, p.80060, 2013. ,
Alternative splicing of the histone demethylase LSD1/KDM1 contributes to the modulation of neurite morphogenesis in the mammalian nervous system, The Journal of neuroscience : the official journal of the Society for Neuroscience, vol.30, issue.7, pp.2521-2553, 2010. ,
Signature-based small molecule screening identifies cytosine arabinoside as an EWS/FLI modulator in Ewing sarcoma, PLoS medicine, vol.4, issue.4, p.122, 2007. ,
A quantitative method for detection of spliced X-box binding protein-1 (XBP1) mRNA as a measure of endoplasmic reticulum (ER) stress. Cell stress & chaperones, vol.17, pp.275-284, 2012. ,
Brefeldin A, thapsigargin, and AIF4-stimulate the accumulation of GRP78 mRNA in a cycloheximide dependent manner, whilst induction by hypoxia is independent of protein synthesis, Journal of cellular physiology, vol.152, issue.3, pp.545-52, 1992. ,
A novel mammalian flavin-dependent histone demethylase, The Journal of biological chemistry, vol.284, issue.26, pp.17775-82, 2009. ,
Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation, Molecular cell, vol.39, issue.2, pp.222-255, 2010. ,
Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution, Nature, vol.518, issue.7539, pp.422-428, 2015. ,
, Cancer Genome Atlas Research N. Comprehensive molecular characterization of urothelial bladder carcinoma, Nature, vol.507, issue.7492, pp.315-337, 2014.
Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer, Nature medicine, vol.22, issue.3, pp.298-305, 2016. ,
Inhibition of histone demethylase, LSD2 (KDM1B), attenuates DNA methylation and increases sensitivity to DNMT inhibitor-induced apoptosis in breast cancer cells, Breast cancer research and treatment, vol.146, issue.1, pp.99-108, 2014. ,
The emerging role of histone lysine demethylases in prostate cancer, Molecular cancer, vol.11, p.52, 2012. ,
PARP-1 inhibition as a targeted strategy to treat Ewing's sarcoma. Cancer research, vol.72, pp.1608-1621, 2012. ,
Recent advances in targeted therapy for Ewing sarcoma, 1000. ,
LSD1 is required for chromosome segregation during mitosis, European journal of cell biology, vol.89, issue.7, pp.557-63, 2010. ,
The lysine demethylase LSD1 is required for nuclear envelope formation at the end of mitosis, Journal of cell science, vol.128, issue.18, pp.3466-77, 2015. ,
Mediators of endoplasmic reticulum stress-induced apoptosis, EMBO reports, vol.7, issue.9, pp.880-885, 2006. ,
Roles of CHOP/GADD153 in endoplasmic reticulum stress, Cell death and differentiation, vol.11, issue.4, pp.381-390, 2004. ,
Magnesium, essential for base excision repair enzymes, inhibits substrate binding of N-methylpurine-DNA glycosylase, The Journal of biological chemistry, vol.281, issue.40, pp.29525-29557, 2006. ,
Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4, Cell death & disease, vol.8, issue.2, p.2631, 2017. ,
Lysine-specific demethylase-1 contributes to malignant behavior by regulation of invasive activity and metabolic shift in esophageal cancer, International journal of cancer Journal international du cancer, vol.138, issue.2, pp.428-467, 2016. ,
LSD1 sustains pancreatic cancer growth via maintaining HIF1alpha-dependent glycolytic process. Cancer letters, vol.347, pp.225-257, 2014. ,
Lysine Demethylase LSD1 Coordinates Glycolytic and Mitochondrial Metabolism in Hepatocellular Carcinoma Cells, Cancer research, vol.75, issue.7, pp.1445-56, 2015. ,
, Data represents mean SP-2509 IC 50 ± SEM from three independent experiments. Open symbols denote most (SK-N-MC) and least (TC-71) SP-2509 sensitive cell lines
, , p.24
, mRNA expression levels of HSPA5, DDIT3, ERN1 and spliced XBP1 in TC252 cells following treatment with DMSO, Thapsigargin (50nM) or SP-2509 (2uM) for the indicated time periods. Data represents mean expression ± SEM from triplicate reactions. (G) PCR analysis of unspliced (XPB1-US) and spliced XBP1 (XPB1-S) in TC252 cells following treatment as in (E), Mol Cancer Ther. Author, p.19, 2019.
, manuscript; available in PMC, Mol Cancer Ther. Author, 2019.