Rogue 'protein factories' point to potential cancer treatments

Cells are packed with proteins, encoded by the recipes in our genes. An EU-funded researcher has discovered key differences in protein production between healthy cells and tumours, revealing exciting potential avenues for the development of future cancer treatments.

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Countries
Countries
  Algeria
  Argentina
  Australia
  Austria
  Bangladesh
  Belarus
  Belgium
  Benin
  Bolivia
  Brazil
  Bulgaria
  Burkina Faso
  Cambodia
  Cameroon
  Canada
  Cape Verde
  Chile
  China
  Colombia
  Costa Rica
  Croatia
  Cyprus
  Czechia
  Denmark
  Ecuador
  Egypt
  Estonia
  Ethiopia
  Faroe Islands
  Finland
  France
  French Polynesia
  Georgia


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Published: 4 December 2018  
Related theme(s) and subtheme(s)
Health & life sciencesMajor diseases  |  Medical research
Human resources & mobilityMarie Curie Actions
Countries involved in the project described in the article
Switzerland
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Rogue 'protein factories' point to potential cancer treatments

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The human body is made up of more than 200 types of cell, from bone and brain to liver and lung. Each cell type is determined by the particular combination of proteins it produces. While skin cells are packed with a sturdy protein called keratin, for example, which gives them their structure, stomach cells produce powerful digestive enzymes to break down food.

Essential processes known as transcription and translation do not work properly in cancer cells, because they contain the wrong amounts and types of proteins. As a result, the cells do not function correctly and they grow out of control to form tumours.

With support from the Marie Curie International Outgoing Fellowship, the SOX project has spent two years studying the precise differences in translation between healthy and cancerous cells, and now aims to turn this knowledge into ideas for potential cancer treatments.

“For the last couple of decades, people have focused on transcription,” says researcher Ataman Sendoel, from the University of Zurich, Switzerland. “We have now learned that translation is as important as transcription in determining cell protein levels.”

Faulty factories

Proteins are produced from recipes encoded within genes. When a particular protein needs to be made, the corresponding gene is ‘read’ to produce a molecular message known as RNA; this process is called transcription. Molecular ‘factories’ inside cells, called ribosomes, then use the instructions in the RNA to put together the correct protein – this is known as translation.

Sendoel’s work has focused on a common type of skin cancer known as squamous cell carcinoma, using mice as a model for the human disease. These cancers are driven by an overactive version of a gene called SOX2, which acts as a kind of ‘immortality factor’ enabling cells to keep growing and multiplying.

Using a technique called ribosome profiling, Sendoel studied exactly what happens when RNA is translated to make protein, looking for crucial differences in the process between healthy cells and squamous cell carcinoma.

He discovered that the ribosomes in the cancer cells switch to an alternative way of producing proteins. Rather than translating the correct RNA messages as they should, they start making unwanted proteins that are associated with cancer growth.

Looking closer, Sendoel found that the key difference lay in a protein called eIF2, which kick-starts the translation process in healthy cells. However, in the cancerous cells this molecule is replaced with an alternative version – known as eIF2A – which drives the production of rogue proteins.

False starts

“If we block this alternative protein production system, then cancers do not form at all,” explains Sendoel. “When we look at patients with squamous cell carcinoma of the head and neck, we find that people whose tumours have higher levels of eIF2A and more alternative protein production have a much shorter overall survival, suggesting that targeting this alternative translation programme could be a good strategy to treat cancer.”

Sendoel is now working on a screening technique to search for drugs that block eIF2A, which could form the basis of future cancer treatments. He is also investigating whether abnormal translation is involved in the growth of other types of cancer.

“We’re a long way from having a drug to use in the clinic and there are so many hurdles in between – but it’s definitely very exciting!”.

Project details

  • Project acronym: SOX
  • Participants: Switzerland (Coordinator)
  • Project N°: 629861
  • Total costs: € 270 964
  • EU contribution: € 270 964
  • Duration: April 2015 to March 2018

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