On the second day of the EMBO 2012 Meeting in Nice, I attended the session on Cell Competition, a fascinating subject that, I must confess, I knew little about before this morning’s symposium.
As Laura Johnston (Columbia University) outlined in her opening talk, cell competition occurs when some cells in a tissue are better able to grow than others. The cells communicate with each other so that the more fit cells – the “winners” – survive and proliferate while the less fit cells – the “losers” – undergo apoptosis. This improves the fitness of the overall tissue and contributes to the regulation of tissue size.
Johnston works on the competition between Drosophila epithelial cells that express different levels of Myc. Overexpressing Myc in some cells makes them outcompete their wild-type neighbors. Depleting Myc from some cells, on the other hand, makes their wild-type neighbors grow faster. Johnston presented some recent studies from her lab investigating how the cells recognize differences in fitness and how the “loser” cells are told to die.
Sergio Casas-Tintó (Cajal Institute, Madrid) and Jean-Paul Vincent (NIMR, London) discussed two different example of competition in Drosophila epithelia induced, respectively, by loss of the actin-binding protein Troponin I and by changes to Wingless signaling. The specific signaling pathways that mediate communication between the “winner” and “loser” cells appear to be different in each case, but the end result is basically the same: the more fit cells survive and grow while the less fit cells die off.
Yasuyuki Fujita (Hokkaido University) gave a nice talk on cell competition in mammalian epithelia, describing how wild-type MDCK cells can eject neighboring transformed cells out of the epithelial layer. Of course, in many cases, transformed cells might pick up mutations that make them more fit than wild-type cells (or other tumor cells with different mutations), and competition is thought to play a key role in tumorigenesis. The session chair, Eduardo Moreno (University of Bern) discussed the role of the “Flower code” in cancer development. Flower is a Drosophila plasma membrane protein that is expressed in two different isoforms: a “Ubi” form that is ubiquitously expressed under normal circumstances, and a “Lose” form that is generated on cells that are growing suboptimally compared to their neighbors and are therefore destined to lose the ensuing competition and die. Moreno reported on his lab’s identification of the mouse Flower homolog and the generation of Flower knockout mice, which should no longer display the phenomenon of cell competition. Moreno showed that a “Lose” isoform of mouse Flower is upregulated in the normal skin surrounding fast-growing papillomas. Flower-deficient mice were protected from papilloma development, however, suggesting that the tumor cells normally rely on the Flower pathway to outcompete neighboring wild-type cells.
As I said, it’s a fascinating subject, and cell competition’s involvement in tumorigenesis seems to be making it an increasingly hot topic – there was certainly competition for seats in the packed seminar room this morning!