Cell cannibalism in tumour samples has been observed for over a century, yet this unusual behaviour is not well studied. New research led by scientists at the Babraham Institute, Cambridge reveals a new mechanism driving cell cannibalism that offers surprising insights into cancer biology.
Cell cannibalism, also called entosis, occurs when one cell surrounds, kills and digests another. Entosis doesn’t typically happen between healthy cells but it is common in tumours. This latest research, published in the journal eLife, reveals that cannibalism can be triggered by cell division; when one cell divides to form two. Since uncontrolled cell division is a key hallmark of cancer, this suggests that cannibalism may have a role to play in resisting cancer.
The research, which also includes scientists from Memorial Sloan Kettering Cancer Centre, USA and the Francis Crick Institute in London, examined human epithelial cells. These cells form many of the surfaces in the body and give rise to over 80% of human cancers. Normally, epithelial cells remain firmly attached to their surroundings when they divide. This study shows that weakened attachments result in more cell cannibalism. This may explain why drugs that weaken cell attachments are effective anti-cancer drugs.
First author on the paper, Dr Jo Durgan, said: “We set out to identify the proteins that control cell cannibalism in tumour cells, but by using time-lapse microscopy to watch this process in action, we stumbled across a completely unexpected new mechanism. The link we’ve found to cell division is really intriguing from the perspective of cancer.”
Cell cannibalism has a complex relationship with cancer and it is not totally clear whether it helps or hinders tumour growth. However, the discovery that dividing cells are more likely to be cannibalised by other cells suggests that entosis may help to slow or prevent cancer by causing cancer cells to be consumed and destroyed by nearby healthy cells.
Lead scientist on the paper, Dr Oliver Florey, said: “Entosis is a fascinating process that may play a role in normal physiology, as well as cancer. By studying entosis, we hope to gain insights into fundamental cell biology, as well as to explore intriguing new avenues for cancer research. After 100 years of observing ‘cell-in-cell’ structures, there is now an exciting push towards discoveries in both cell and cancer biology.”
Durgan J, Tseng Y-Y, Hamann JC, Domart M-C, Collinson L, Hall A, Overholtzer M, Florey O (2017) Mitosis can drive cell cannibalism through entosis. eLife. https://doi.org/10.7554/eLife.27134
Joanne Durgan was funded by a Revson Senior Fellowship in the Biomedical Sciences, a Marie-Curie Fellowship and a L’Oreal for Women in Science UK award. Lucy Collinson by Cancer Research UK, the MRC, Wellcome Trust, BBSRC and EPSRC. Michael Overholtzer by the National Cancer Institute and Oliver Florey by Cancer Research UK. This work was also supported by the friends and family of Jean Florey, who donated in her memory.
Dr Jonathan Lawson, Babraham Institute Communications Manager email@example.com
Top image: Two cells (right and left) competing to consume a third cell, which is in the process of dividing (centre). DNA is labelled blue in all cells and is arranged differently in the dividing cell. A protein called β-catenin, which forms contacts between two cells, is shown in green.
Left: A dividing cell (bottom right) being cannibalised by another cell (centre).
Right: A dividing cell that has been engulfed by another cell.
Colours as described above.
Affiliated Authors (in author order):
Joanne Durgan, Signalling Programme, Babraham Institute
Oliver Florey, Group Leader, Signalling Programme, Babraham Institute
About the Babraham Institute:
The Babraham Institute receives strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) to undertake world-class life sciences research. Its goal is to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Research focuses on signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing.
11 July 2017