Related Experiment Video
Updated: Aug 6, 2026
12:03
In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis
Published on: December 9, 2016
Proinflammatory signaling in Ewing sarcoma is driven by retroelement activity and counteracted by reverse
Valentina Evdokimova1, Peter Ruzanov1, Hendrik Gassmann2
1Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
Cell Reports
|July 21, 2026
Summary
Endogenous retroviral elements (EREs) drive inflammation and immune suppression in Ewing sarcoma (EwS). Targeting reverse transcriptase activity with inhibitors may offer a new therapeutic strategy for this childhood cancer.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Ewing sarcoma (EwS) is a pediatric cancer driven by EWS::FLI1 fusion proteins.
- EwS exhibits a complex inflammatory and immunosuppressive tumor microenvironment.
Purpose of the Study:
- To investigate the role of endogenous retroviral elements (EREs) in EwS-associated inflammation and immunosuppression.
- To explore potential therapeutic strategies targeting EREs.
Main Methods:
- Analysis of ERE expression in EwS tumor cells and extracellular vesicles (EVs).
- Assessment of EREs' impact on monocytes and stromal cells.
- Evaluation of reverse transcriptase (RT) activity and downstream signaling pathways (cGAS-IFN-I, STAT3, NF-κB).
- Testing the efficacy of RT inhibitors (abacavir, lamivudine) in preclinical models.
Main Results:
- LINE, SINE, and LTR/HERV EREs are highly expressed in EwS and linked to EWS::FLI1.
- Disseminated EREs in EVs induce inflammation and immunosuppression in target cells.
- Certain EREs (LINE-1, HERV-K) encode proteins and exhibit RT activity, activating inflammatory pathways.
- RT inhibitors reduced RT activity, inflammation, and cytokine release.
Conclusions:
- EREs are key drivers of inflammation and immunosuppression in Ewing sarcoma.
- Targeting ERE reverse transcriptase activity represents a promising therapeutic avenue for EwS.
Keywords:
CP: cancerEwing sarcomaHERV-KIFN-ILINE-1NFkBSTAT3TBK1cGAScytokinesendogenous retroelementextracellular vesiclesinflammationreverse transcriptaseMore Related Videos
Related Concept Videos
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.
03:18Non-LTR Retrotransposons
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
01:03Rous Sarcoma Virus (RSV) and Cancer
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
01:51Mechanisms of Retrovirus-induced Cancers
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
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...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...