Related Experiment Video
Updated: Jul 9, 2026
09:58
Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
The EWS/FLI1 oncogenic transcription factor deregulates GLI1
J P Zwerner1, J Joo, K L Warner
1Department of Dermatology, Stanford University School of Medicine, Palo Alto, CA, USA.
Oncogene
|December 18, 2007
Summary
The EWS/FLI1 fusion gene in Ewing family tumors upregulates GLI1, a key driver of tumor growth. Inhibiting GLI1 reduces tumor transformation activity, suggesting it
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ewing family tumors (EFT) are characterized by specific fusion genes.
- The EWS/FLI1 fusion is the most common genetic alteration in EFT.
- These fusion genes are believed to be critical in driving tumor development.
Purpose of the Study:
- To investigate the role of GLI1 in EFT pathogenesis.
- To determine if EWS/FLI1 directly regulates GLI1 expression.
- To assess the therapeutic potential of targeting GLI1 in EFT.
Main Methods:
- Utilized a model transformation system to study EWS/FLI1 effects.
- Employed RNA interference (RNAi) to inhibit GLI1.
- Analyzed GLI1 and PATCHED1 expression in EFT cell lines.
- Investigated the role of cMYC and Hedgehog signaling pathways.
Main Results:
- EWS/FLI1 upregulates GLI1 and its target PATCHED1 in a model system.
- GLI1 deregulation is dependent on EWS/FLI1 functional domains.
- Inhibition of GLI1 reduces EWS/FLI1-mediated transformation.
- GLI1 activation is largely Hedgehog-independent.
- EWS/FLI1-dependent GLI1 and PATCHED1 expression observed in EFT cells.
- GLI1 inhibition reduces anchorage-independent growth in EFT cells.
Conclusions:
- GLI1 is a transcriptionally deregulated target of EWS/FLI1 in EFT.
- GLI1 mediates a portion of the tumorigenic phenotype driven by EWS/FLI1.
- Targeting GLI1 represents a potential therapeutic strategy for EFT.
Related Concept Videos
01:06Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Somatic cells are...
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:54Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...