It is expected this discovery will have a positive impact on the fundamental understanding of how cancer cells may begin and continue to grow and could lead to better and more targeted treatments for cancer.

The research has been published in the journal Science Advances.

The human genome is packaged into chromatin, which is composed of proteins that help control gene expression, DNA replication and repair, and genome stability. In recent years, it has become clear that the deregulation of this chromatin structure plays an important role in numerous cancers.

Chromatin proteins can add specific chemical modifications which determine when and how genes are turned on and off. Previous research has shown that a gene called USP7 is a key player in cancer. However, until now, the exact mechanism for this has not been fully understood by scientists.

This new research has discovered that USP7 regulates the stability of a key chromatin protein complex called PRC1.6, which in turn increases the level of a specific chemical modification called H2AK119Ub. The study found that this USP7-PRC1.6-H2Ak119Ub molecular axis is important for turning off gene expression and controlling cell identity in cancer cells.

Co-lead author, Dr Yaser Atlasi, Principal Investigator on the research and Illuminate Vice-Chancellor’s Fellow at The Patrick G Johnston Centre for Cancer Research at Queen’s University Belfast, explains: “In order to tackle cancer, it is crucial we understand the many features of our genome and how it is regulated by associated proteins within our cells. By identifying the link between the USP7 gene and genome activity in cancer cells, our findings open the possibility of providing better and more targeted treatments for cancer.”

Professor Peter Verrijzer, from Erasmus University Medical Centre Rotterdam, said: “USP7 is involved in both tumor suppression and in neurodevelopmental disorders. Our research identified novel crucial targets of USP7, thereby providing a roadmap for potential therapeutic intervention in these diseases.”

The next step of the research is to understand how this epigenetic axis controls the cellular identity in normal stem cells and in cancer cells that have stem cell features (cancer stem cells). Furthermore, the researchers will investigate how targeting this axis in combination with standard care therapies can enhance treatment effectiveness for people with cancer.

The international team includes researchers from Queen’s University Belfast and Erasmus Medical Center, Rotterdam.

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