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Eugenia Piddini

piddini2013Eugenia Piddini PhD, Royal Society Research Fellow, Member of the Department of Zoology.

Europe PMC | Pubmed

 

 

 

 

Cell competition in normal physiology and cancer

2016 PiddiniCan we learn how to exploit cell competition to design new therapies? Competitive interactions occur between cells in tissues, resulting in fit cells (winners) being able to colonise tissues as they kill and replace less-fit cells (losers).

We are exploring how cell competition could be harnessed for therapeutic strategies in regenerative medicine and cancer. Towards that aim, our goal is to understand the impact of cell competition on tissues and the mechanisms that cells use to compete. We combine two complementary approaches: studies in Drosophila to capture the complexity of these interactions in vivo, and mammalian cell culture to follow the dynamics of cell competition, including by live imaging.

Our recent work using the adult fly intestine shows that in adult homeostatic tissues, cells compete and healthy cells eliminate subfit cells by apoptosis. Conversely, we found that cell competition leads to healthy tissue expansion, by promoting stem cell proliferation and increased symmetric self-renewal. We believe that this could be exploited to promote stem cell repopulation in regenerative medicine therapies.

Selected publications:

• 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. (2016) Mechanical cell competition kills cells via induction of lethal p53 levels. Nature Communications 7:11373  DOI: 10.1038/NCOMMS11373.

• Suijkerbuijk SJE, Kolahgar G, Kucinski I, Piddini E. (2016) Cell competition drives the growth of intestinal adenomas in Drosophila. Current Biology 26(4):428-38. 

• Kolahgar G, Suijkerbuijk SJE, Poirier E, Mansour S, Simons BD and Piddini, E. (2015) Cell competition modifies adult stem cell and tissue population dynamics in a JAK-STAT dependent manner. Developmental Cell 34(3):297-309. Featured Article

•  Graml V, Studera X, Lawson JL, Chessel A, Geymonat M, Bortfeld-Miller M, Walter T, Wagstaff L, Piddini E, Carazo-Salas RE. (2014) A genomic multi-process survey of the machineries that control and link cell shape, microtubule organisation and cell cycle progression. Developmental Cell 31(2):227–239.

• Wagstaff L, Kolahgar G, and Piddini E. (2013) Competitive cell interactions in cancer: a cellular tug of war. Review. Trends in Cell Biology 23:160–167. 

• Vincent JP*, Kolahgar G, Gagliardi M and Piddini E*. (2011) Steep differences in Wingless signalling trigger Myc-independent competitive cell interactions. Developmental Cell  21:366-374.

*Corresponding authors

groupPiddini2015

Plain English

For tissues in our body to function optimally, the cells that they are made of must also perform optimally. To achieve this, a mechanism has evolved called ‘cell competition’, which occurs during embryonic development. In essence, when tissues are first formed, as cells grow and divide they compare their fitness with neighbour cells and those cells that are sensed as weaker die and are eliminated, such that only the best cells give rise to the tissue. Cell competition can thus be seen as one of the processes that ensures the birth of healthy individuals.

However, good things can sometimes be used for a bad cause and this seems true for cell competition, which recent studies suggest could be involved in cancer, by allowing cancer cells to kill surrounding normal cells and boosting their own tissue colonization. 

How do cells actually compete? What signals do they use to sense which cells are stronger? What molecules are activated in the weaker cells to trigger their death? We aim to shed light on these questions in order to understand this fundamental biological phenomenon and its impact on cancer biology and tissue maintenance.

Co-workers

Michael Dinan • Maja Goschorska • Golnar Kolahgar • Kasia Kozyrska • Paola Marco Casanova • Kathy Oswald