Eugenia Piddini PhD, Royal Society Research Fellow, Member of the Department of Zoology.
Cell competition in normal physiology and cancer
The elimination of suboptimal cells from tissues is an important process that helps preserve tissue integrity and function. Cells within tissues compare relative fitness and, when viable but suboptimal cells are present, they are eliminated by fitter neighbouring cells through competitive cell interactions. Much of the work in our lab focuses on investigating the mechanisms and the physiological role of competitive cell interactions.
Cell competition has been studied mostly in developing tissues and currently it is not clear to what extent this phenomenon is relevant to adult tissues. We are investigating whether adult tissues monitor and respond to the presence of cells with compromised fitness. This would have important implications, as selection of fitter cells during adult tissue maintenance could lead to improved tissue fitness and play a role in slowing down tissue ageing. Our model system for these studies is the adult Drosophila gut, a simple epithelial layer with high cellular turnover, maintained by a pool of stem cells. Our recent data show that in adult tissues weaker cells are detected and eliminated through apoptosis and that this is accompanied by an increase in stem cell numbers and tissue colonisation properties in the fitter cell population.
Competitive cell interactions could play a role in cancer. Indeed it has been suggested that precancerous cells could act as supercompetitors and kill surrounding normal cells, to make more space for themselves. However, it has also been observed that cells carrying some tumour promoting mutations can be eliminated by wild-type cells, suggesting that cell competition could in some instances aid cancer prevention. Our lab is establishing in vitro assays to study these complex interactions between tumour cells and normal cells.
• Wagstaff L, Goschorska M, Kozyrska K, Duclos G, Kucinski I, Chessel A, Hampton-O’Neil L, Bradshaw CR, Allen GE, Rawlins EL, Silberzan P, Carazo Salas RE and Piddini E. Mechanical cell competition kills cells via induction of lethal p53 levels. Nature Communications 2016, 7, 11373
• Suijkerbuijk SJE, Kolahgar G, Kucinski I, Piddini E. Cell competition drives the growth of intestinal adenomas in Drosophila. Current Biology 2016 Feb 22;26(4):428-38.
• Kolahgar G, Suijkerbuijk SJE, Poirier E, Mansour S, Simons BD and Piddini, E. Cell competition modifies adult stem cell and tissue population dynamics in a JAK-STAT dependent manner. Developmental Cell 2015 Aug 10;34(3):297-309 Featured Article
• Wagstaff L., Kolahgar G, and Piddini E. Competitive cell interactions in cancer: a cellular tug of war. Review. Trends in Cell Biology 2013, 23, 160–167
• Vincent JP*, Kolahgar G, Gagliardi M and Piddini E*. Steep differences in Wingless signalling trigger Myc-independent competitive cell interactions. Developmental Cell 2011 21, 366-374. *Corresponding authors