ArticleOncotarget2015
PI3K/AKT signaling modulates transcriptional expression of EWS/FLI1 through specificity protein 1.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Targeted and molecular therapies in Ewing sarcoma: a comprehensive review of preclinical and clinical advances.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Regulation of EWSR1-FLI1 Function by Post-Transcriptional and Post-Translational Modifications.Cancers · 2023Review
- TrkC, a novel prognostic marker, induces and maintains cell survival and metastatic dissemination of Ewing sarcoma by inhibiting EWSR1-FLI1 degradation.Cell death & disease · 2022Article
- Schlafen 11 expression in human acute leukemia cells with gain-of-function mutations in the interferon-JAK signaling pathway.iScience · 2021Article
- Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma.Oncogene · 2021Article
- The Role of Tyrosine Kinases as a Critical Prognostic Parameter and Its Targeted Therapies in Ewing Sarcoma.Frontiers in cell and developmental biology · 2020Review
- Genetics and Epigenetics of Gastroenteropancreatic Neuroendocrine Neoplasms.Endocrine reviews · 2019Review
- USP19 deubiquitinates EWS-FLI1 to regulate Ewing sarcoma growth.Scientific reports · 2019Article
- Article
- Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium.The Journal of endocrinology · 2018Review
- Therapeutic targeting of PGBD5-induced DNA repair dependency in pediatric solid tumors.Science translational medicine · 2017Article
- Targeting specificity protein 1 transcription factor and survivin using tolfenamic acid for inhibiting Ewing sarcoma cell growth.Investigational new drugs · 2017Article
- Targeting the EWS-ETS transcriptional program by BET bromodomain inhibition in Ewing sarcoma.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ewing sarcoma (ES) is the second most frequent bone cancer in childhood and is characterized by the presence of the balanced translocation t(11;22)(q24;q12) in more than 85% of cases, generating a dysregulated transcription factor EWS/FLI1. This fusion protein is an essential oncogenic component of ES development which is necessary for tumor cell maintenance and represents an attractive therapeutic target. To search for modulators of EWS/FLI1 activity we screened a library of 153 targeted compounds and identified inhibitors of the PI3K pathway to directly modulate EWS/FLI1 transcription. Surprisingly, treatment of four different ES cell lines with BEZ235 resulted in down regulation of EWS/FLI1 mRNA and protein by ~50% with subsequent modulation of target gene expression. Analysis of the EWS/FLI1 promoter region (-2239/+67) using various deletion constructs identified two 14 bp minimal elements as being important for EWS/FLI1 transcription. We identified SP1 as modulator of EWS/FLI1 gene expression and demonstrated direct binding to one of these regions in the EWS/FLI1 promoter by EMSA and ChIP experiments. These results provide the first insights on the transcriptional regulation of EWS/FLI1, an area that has not been investigated so far, and offer an additional molecular explanation for the known sensitivity of ES cell lines to PI3K inhibition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.