Eugenia Piddini PhD, Royal Society Research Fellow, Member of the Department of Zoology.
Competitive cell interactions 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.
• 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
• Vivarelli S, Wagstaff L and Piddini E (2012) Cell wars: regulation of cell survival and proliferation by cell competition. (Review) Essays Biochem. (Review Essays Biochemistry 2012 Aug 10;53(1):69-82.
• Hogan C, Dupré-Crochet S, Norman M, Kajita M, Zimmermann C, Pelling AE, Piddini E, Baena-López LA, Vincent JP, Itoh Y, Hosoya H, Pichaud F, Fujita Y (2009) Characterisation of the interface between normal and transformed epithelial cells. Nature Cell Biology Apr;11(4):460-7
• Piddini E and Vincent JP (2009) Interpretation of the Wingless gradient requires signalling-induced self-inhibition. Cell Jan 136, 296-307