Researchers uncover crucial gene for growth of Ewing sarcoma

October 23, 2020

Researchers at the Institut de Recerca Sant Joan de Déu (IRSJD) in collaboration with those at Centre for Genomic Regulation (CRG) have discovered that RING1B is a critical gene for the development of Ewing sarcoma, a rare type of developmental cancer that presents in bones and soft tissues. This newly uncovered epigenetic vulnerability in Ewing sarcoma cancer cells opens the door for new therapeutic strategies.

Ewing sarcoma is caused by a chromosomal translocation, where the EWSR1 gene in chromosome 22 fuses with most commonly the FLI1 gene in chromosome 11. The resulting EWSR1-FLI1 fusion protein, which contains the transcriptional activation machinery of EWSR1 and the DNA-binding domain of FLI1, is the main driver of tumorigenesis.

A new study published today in Science Advances describes how the oncogenic EWSR1-FLI1 fusion protein is directed to the different parts of the genome by RING1B, allowing EWSR1-FLI1 to hijack the transcriptional program of the cells, turning them into cancerous cells.

Researchers found that RING1B and EWSR1-FLI1 localize at the same regions in the genome, where RING1B is responsible for EWSR1-FLI1 recruitment. EWSR1-FLI1 cannot activate its target genes and transform a cell from healthy to cancerous state without RING1B, as shown by impaired tumour growth when RING1B is reduced.

Epigenetic inhibitors have been previously proposed to treat Ewing sarcoma and other types of paediatric cancers such as neuroblastoma, rhabdomyosarcoma or synovial sarcoma. Further research could explore the pharmacological inhibition of RING1B as a clinical therapy to treat Ewing sarcoma.

"Our findings offer striking insights into the mechanism of Ewing sarcoma, helping us get closer to uncovering the elusive cell-of-origin for this rare type of cancer," says Luciano Di Croce, researcher at the Centre for Genomic Regulation and one of the authors of the study. "All we have to do is look for high levels of RING1B."

"EWSR1-FLI1 remains a challenging druggable target, therefore understanding its dependencies may offer alternative strategies to switch off its aberrant transcriptional program," says Sara Sánchez-Molina, first author of the study and postdoctoral researcher at the Institut de Recerca Sant Joan de Déu.

"Ewing tumors are paradigmatic examples of developmental cancers, where the first hit (genetic or epigenetic) occurs during embryonic development (gestation) and, in the majority of Ewing sarcomas, develops postnatally during specific stages of growth like puberty. The study supports the model by which embryonic stem cells characterized by high levels of RING1B are capable to sustain the aberrant transcriptional program caused by the oncogenic fusion protein. Ewing sarcoma will develop if the individual is born with precursor cells bearing the fusion oncoprotein", says Jaume Mora, Scientific Director of the Pediatric Cancer Center Barcelona-Institut de Recerca Sant Joan de Déu, and director of the study.
-end-


Center for Genomic Regulation

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.