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25
Feb
2019

Cell death triggers keep cancer at bay in healthy cells

Lung cancer cells dividing

Image: A lung cancer cell in the latter stages of cell division where the two daughter cells have nearly separated from each other; only a small bridge of cytoplasm connects them. Credit: Anne Weston, Francis Crick Institute. License: CC BY-NC 4.0

Two molecules with the power of life and death over cells also play a key role in protecting the genome and preventing cancer, a major new study reveals.

Scientists at The Institute of Cancer Research, London, showed that the proteins, called RIPK1 and Casp8, work together to copy DNA correctly when cells divide.

The two proteins are known for their role in triggering cell death, but the study found they also seem to act as ‘tumour suppressors’, preventing healthy cells becoming cancerous by stopping the genetic faults that trigger cancer.

This unexpected role – revealed in research published in Molecular Cell – could help to explain why the proteins can be missing or damaged in several forms of cancer.

Maintaining chromosome stability

During the process of cell division, the DNA in our cells containing instructions for building every part of our bodies must be copied exactly to produce two healthy and identical daughter cells.

The cell forms two copies of its chromosomes – the packages of DNA – before lining them up in preparation to divide.

If the chromosomes aren’t lined up properly, the daughter cells can have too many chromosomes or too few, or other mistakes that can lead to cancer.

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The researchers found that RIPK1 and Casp8 come together to form a larger protein structure that helps chromosomes line up during cell division.

Cells treated with agents that disrupt RIPK1 and Casp8 activity caused chromosomes to become misaligned during this process.

They deleted the proteins from cells in mice, and found that many cells displayed chromosome alignment defects in the absence of either protein.

Chromosome instability is a defining feature of cancer, so understanding how these proteins work together could uncover new ways to treat the disease.

“Staving off cancer”

The research was supported by Breast Cancer Now, the Medical Research Council and the NIHR Biomedical Research Centre at The Royal Marsden and the ICR.

Study author Professor Pascal Meier, Leader of the Cell Death Inflammation Team at the ICR, said:

“Our study sheds light on the biological processes that help determine whether a cell is healthy or could become cancerous. Our research suggests that Casp8 and RIPK1 help keep our chromosomes stable – staving off cancer.

“Loss of function of these proteins is linked to a range of cancers and degenerative diseases, and learning more about them could lead us to new cancer treatments.”

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Pascal Meier Breast Cancer Now Breast Cancer Research Cell Death and Inflammation
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