Sydney research discovery could lead to new cancer therapies

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Researchers at Children’s Medical Research Institute (CMRI) in Westmead, Sydney, say they have made an unexpected discovery about cancer cells.

The researchers say the finding, published today in Nature Cell Biology, could support new efforts to produce tailored therapies to kill cancer cells.

Dr Noa Lamm, lead scientist on this project, has spent several years working on the research that has revealed an unexpected function for the protein actin.

Actin is the protein that interacts with another called myosin to make muscles contract. Actin also forms cables inside cells that connect and function like girders in a building, contributing to the structure and shape of cells.

Scientists have known for several decades that actin plays this critical role in the main body of the cell. However, its role in the cell's control centre, the nucleus, has been considered controversial.

For cancers to grow, cancer cells need to make many new copies of themselves. Every time this happens, the DNA in the cancer cells' nuclei must be replicated.

“Whether actin played a role in DNA replication was not known,’’ said Dr Lamm

DNA replication in a cancer cell frequently breaks down and has to get restarted. Cancer chemotherapy exploits this weakness in cancer cells by making the process break down more frequently in an attempt to destroy them.

Dr Lamm found that when cancer cells encounter problems replicating their DNA, actin cables form inside the nucleus. This allows the nucleus to change shape and increases the ability of the cancer cell to repair its DNA and restart the replication process.

Using advanced super-resolution microscopy, the researchers showed that damaged DNA slides along the actin network to move to areas in the nucleus where repair occurs most efficiently. Scientists were previously unaware that cancer cells protected themselves in this way. Critically, this research found that actin performed these unexpected functions in response to treatment with chemotherapy and helped cancer cells resist the treatment.

Dr Lamm believes there are two ways this discovery will help cancer patients. First, treatments that disable the actin cable mechanism could kill cancers that already have difficulty maintaining a high rate of DNA replication. Second, adding treatment that interferes with the actin cables to commonly used chemotherapies will enhance their success rate.

Dr Lamm added, “Science is very creative; you get the feeling that you are doing something that no one else is, because no two scientists will ask exactly the same questions. It’s exciting to understand something that was not known before.

“We are very hopeful this will be a big step forward, because all progress starts with basic discovery.’’

Dr Lamm is a part of the team from the University of Sydney’s Faculty of Medicine and Health.

CMRI researchers working on this project include Dr Lamm, Associate Professor Tony Cesare, Dr David Ly, Scott Page and Dr Pragathi Masamsetti. They worked with Dr Mark Reed from The University of Sydney, Professor Paul Timpson and Dr Max Nobis of The Garvan Institute, and Dr Maté Biro from the University of NSW.