Scientists identify potential target for treating rare cancer

November 27, 2018

Researchers have pinpointed a protein that plays a key role in a type of rare cancer often leading to tumours around joints and tendons, according to new findings in eLife.

Their study in mice suggests that degradation of the BRD9 protein could block tumour progression of synovial sarcoma tumours.

Also known as malignant synovioma, synovial sarcoma is an aggressive soft-tissue sarcoma that can occur anywhere in the body, including the brain, prostate and heart, but often appears near the knee. While it may not cause any noticeable signs or symptoms at first, development of the tumour can cause a lump or swelling and, in some cases, numbness or pain if it presses on nerves.

"Synovial sarcoma tumours contain a characteristic fusion protein, called SS18-SSX, which drives disease development," explains first author and Research Fellow Gerard Brien, who led the research with a team from Scott Armstrong's lab when he was at the Dana-Farber Cancer Institute, US. "Targeting such proteins presents an attractive therapeutic opportunity, but SS18-SSX has previously proven difficult to exploit for drug development purposes."

Using a custom CRISPR/Cas9 screen, Brien and his team identified that the BRD9 protein is critical to the continued growth and survival of synovial sarcoma cells.

"We found that BRD9 is a component of SS18-SSX containing SWI/SNF protein complexes in synovial sarcoma cells," Brien explains. "Moreover, integration of BRD9 into these complexes is critical for synovial sarcoma cells to grow."

The team developed a novel small-molecule degrader of BRD9 function and used it to target the protein. Remarkably, they found that synovial sarcoma cells are highly sensitive to the molecule, while other sarcoma subtypes are unaffected by it. When the molecule degrades BRD9 in synovial sarcoma, it subsequently inhibits tumour progression.

"We've highlighted BRD9 as the first actionable therapeutic target in synovial sarcoma tumours that is linked both biochemically and functionally to SS18-SSX," concludes senior author Scott Armstrong, Chairman of the Department of Pediatric Oncology at the Dana-Farber Cancer Institute. "Our work paves the way for future investigation into how BRD9 degradation could be exploited for developing novel treatments against the disease."
-end-
Reference

The paper 'Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma' can be freely accessed online at https://doi.org/10.7554/eLife.41305. Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

Media contact

Emily Packer, Senior Press Officer
eLife
e.packer@elifesciences.org
01223 855373

About eLife

eLife aims to help scientists accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours in science. We publish important research in all areas of the life and biomedical sciences, including Biochemistry and Chemical Biology and Cancer Biology, which is selected and evaluated by working scientists and made freely available online without delay. eLife also invests in innovation through open-source tool development to accelerate research communication and discovery. Our work is guided by the communities we serve. eLife is supported by the Howard Hughes Medical Institute, the Max Planck Society, the Wellcome Trust and the Knut and Alice Wallenberg Foundation. Learn more at https://elifesciences.org/about.

To read the latest Biochemistry and Cancer Biology research published in eLife, visit https://elifesciences.org/subjects/biochemistry-chemical-biology and https://elifesciences.org/subjects/cancer-biology.

eLife

Related Protein Articles from Brightsurf:

The protein dress of a neuron
New method marks proteins and reveals the receptors in which neurons are dressed

Memory protein
When UC Santa Barbara materials scientist Omar Saleh and graduate student Ian Morgan sought to understand the mechanical behaviors of disordered proteins in the lab, they expected that after being stretched, one particular model protein would snap back instantaneously, like a rubber band.

Diets high in protein, particularly plant protein, linked to lower risk of death
Diets high in protein, particularly plant protein, are associated with a lower risk of death from any cause, finds an analysis of the latest evidence published by The BMJ today.

A new understanding of protein movement
A team of UD engineers has uncovered the role of surface diffusion in protein transport, which could aid biopharmaceutical processing.

A new biotinylation enzyme for analyzing protein-protein interactions
Proteins play roles by interacting with various other proteins. Therefore, interaction analysis is an indispensable technique for studying the function of proteins.

Substituting the next-best protein
Children born with Duchenne muscular dystrophy have a mutation in the X-chromosome gene that would normally code for dystrophin, a protein that provides structural integrity to skeletal muscles.

A direct protein-to-protein binding couples cell survival to cell proliferation
The regulators of apoptosis watch over cell replication and the decision to enter the cell cycle.

A protein that controls inflammation
A study by the research team of Prof. Geert van Loo (VIB-UGent Center for Inflammation Research) has unraveled a critical molecular mechanism behind autoimmune and inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis.

Resurrecting ancient protein partners reveals origin of protein regulation
After reconstructing the ancient forms of two cellular proteins, scientists discovered the earliest known instance of a complex form of protein regulation.

Sensing protein wellbeing
The folding state of the proteins in live cells often reflect the cell's general health.

Read More: Protein News and Protein 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.