Entosis is a recently discovered process of live cell engulfment in which one epithelial cell is completely internalised by another, forming a 'cell-in-cell' structure. The majority of engulfed cells are killed and digested by their host, in an unusual form of cellular cannibalism. Entosis is commonly observed in human tumours and entotic cell killing represents a novel mode of tumour suppression. Although cell-in-cell structures have been noted by pathologists for decades, the molecular and cellular mechanisms that drive entosis remain poorly understood. Further study of this emerging topic will advance our understanding of both cell and cancer biology.
Entosis typically occurs under conditions of matrix detachment. However, I have discovered that mitosis can drive entosis in adherent cells (unpublished). The potential significance of this observation to cancer is striking, given the highly proliferative nature of cells within a tumour. Entotic cell killing may provide a means to limit inappropriately dividing cells. In the proposed work, we will pursue this novel finding by studying the:
1) Molecular mechanisms that promote mitosis-induced entosis
2) Biophysical changes which accompany mitosis to induce entosis (multidisciplinary, international collaboration)
3) Occurrence and significance of mitosis-induced entosis in human cancer
4) Relevance of entosis to anti-mitotic cancer therapies
The host lab is one of a few groups globally with experience in studying entosis and the Babraham Institute provides a rich research environment, with state of the art equipment. I will bring my key preliminary data and >10 years experience in biochemical/cell biological studies to aid this work and transfer knowledge to my host. We will also work collaboratively with Dr Michael Overholtzer (USA), who discovered entosis. By combining our expertise, we will gain valuable insight into the intriguing process of mitosis-induced entosis and its role in cancer.
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