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‘How can we translate the language of cells into cancer therapies?’

On 23 April 2021, Professor Alfred Vertegaal from the Department of Cell and Chemical Biology at the Leiden University Medical Center (LUMC) delivered his inaugural lecture ‘Unraveling and exploiting cellular communication codes’. Vertegaal used the opportunity to describe how research in the field of cell biology can help translate the language of cells into cancer therapies.

Any type of information exchange between living organisms is a form of communication. As the basic units of life, cells exchange information through a special code-mediated language called ‘post-translational protein modifications’ (PTMs). Vertegaal explains: ‘Many cell biologists are interested in deciphering PTM codes because they can be translated into a broad array of therapies for cancer and other diseases.’

Language for cell division

On average, an adult human being consists of about 37 trillion cells that are diverse in form and function. As part of the continuous cell replacement programme that is crucial to keeping our organs vital, billions of cells will divide in our bodies every day. Communication between cells is key to ensuring that such large numbers of divisions and differentiations are well coordinated. Vertegaal: ‘PTMs are the language that regulates cellular division. We have learned about different PTM “dialects”, such as SUMOylation, ubiquitination and phosphorylation. Much research is still needed to fully understand how these dialects work together to orchestrate cell division and other molecular processes. PTMs form a dynamic information exchange network that is extremely complex – like metro networks in some of the world’s major cities. In the coming years, we want to gain further knowledge of how they converse using mass spectrometry.”

Thirty kilometres of spaghetti

Vertegaal’s research team is focusing in particular on the role of SUMOylation and its interaction with other PTMs. ‘It’s a big challenge for the cell to fit the long strands of DNA – the hereditary material that contains instructions on how to build other cells – into a tiny nucleus without damaging them. It would be the equivalent to fitting 30 kilometers of spaghetti onto a dinner plate,’ he says. SUMO enables cells to correctly fold DNA and distribute it among daughter cells. 

‘Our group is currently investigating why cell division does not work without SUMO,’ Vertegaal says. His team had previously discovered that inhibiting SUMOylation hinders cell growth and the division process. ‘We observed how the distribution of chromosome copies between daughter cells becomes prone to errors that cause damage to the DNA.’ This research has not only delivered insights on cellular division mechanisms, but is studies are providing new horizons for cancer therapies.

PTM inhibitor therapies 

Vertegaal: ‘A lot of work is currently being done on anti-cancer drugs that intervene at the PTM level, such as PTM enzyme inhibitors. Inhibitor therapies do pose significant challenges though because they also affect healthy cells that need to divide.’ Cancer cells nonetheless have distinctive features that can be exploited by these drugs. ‘SUMO inhibitors have previously proven useful when treating certain types of cancer in petri dishes, and are now being tested on patients. This is an exciting phase of the research, and understanding the language of cells is crucial in our aim to help patients by finding out which types of cancer are sensitive to PTM therapies.’

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