A5040783934- Sarcoma Diagnosis and Treatment
- Hippo pathway signaling and YAP/TAZ
- Protein Degradation and Inhibitors
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- interferon and immune responses
- Cancer, Hypoxia, and Metabolism
St Anna Children's Hospital
2023-2025
St. Anna Children's Cancer Research Institute
2023-2025
Ewing sarcoma (EwS) is an aggressive cancer of adolescents in need effective treatment. Insulin-like growth factor (IGF)-1 autocrine for EwS, but only 10% patients respond to IGF-1 receptor (IGF-1R) blockade. Although EwS presumed originate from mesenchymal progenitors during bone development, targeting the driver oncogene EWS::FLI1 lineage a mouse model does not result tumor formation skeletal malformations and perinatal death. We report that transient exposure concentrations mimicking...
The mechanisms underlying tumor cell plasticity driving drug resistance and disease progression remain poorly understood. In Ewing sarcoma (EwS), variations in EWS::FLI1 (EF) activity have been associated with epithelial-mesenchymal (EMP). Using degron technology, we titrated endogenous EF an EwS line linked phenotypic states to distinct thresholds. Strikingly, modest depletion promoted a pro-metastatic phenotype, that diminished upon near-complete loss. Nascent RNA sequencing revealed gene...
Abstract Ewing sarcoma (EwS) is a highly aggressive pediatric cancer driven by the EWS::FLI1 (EF) fusion oncoprotein. Emerging evidence suggests that variations in EF expression levels may contribute to tumor cell plasticity, promoting treatment resistance and relapse. Both intrinsic extrinsic influences such as microenvironmental therapy related factors, influence thresholds. However, phenotypic consequences of fluctuations at different amplitudes intervals remain poorly understood. To...
Abstract Ewing sarcoma (EwS) is an aggressive cancer of adolescents in need effective treatments. Insulin like growth factor (IGF) 1 was previously reported autocrine for EwS, but only 10% patients responded to IGF-1 receptor blockade. Although presumed originate from mesenchymal progenitors during bone development, targeting the EwS driver oncogene EWS::FLI1 lineage a conditional mouse model did not result tumor formation led skeletal malformations and perinatal death. We report that...
Abstract Ewing sarcoma is a highly aggressive pediatric cancer driven by the EWS::FLI1 (EF) fusion oncogene. Evidence suggests that EF expression levels dictate tumor cell plasticity contributing to treatment resistance and relapse. Our study aims elucidate transcriptional programs phenotypes associated with distinct thresholds. To dynamically fine-tune levels, we engineered line models C-terminally tagging endogenous fluorescent (mNG) degron tag (dTAG). Using mNG as quantitative proxy for...
Abstract Ewing sarcoma (ES) is a rare, highly aggressive cancer of the bone and soft tissues that mainly affects children young adults. The most common driver ES chromosomal translocation between EWSR1 gene an ETS family member, frequently FLI1. This leads to expression aberrant transcription factor called EWS::FLI1 (EF1) acts as epigenetic reprogrammer transcriptional modulator. Previous studies on cell lines showed EF1 levels are dynamic where cells with high more proliferative, while low...