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Lolo F.-N.,Spanish National Cancer Center | Lolo F.-N.,Spanish National Cardiovascular Center | Tinto S.C.,Spanish National Cancer Center | Tinto S.C.,Cajal Institute CSIC | And 2 more authors.
BioEssays | Year: 2013

Recent results show that, during the process known as cell competition, winner cells identify and kill viable cells from a growing population without requiring engulfment. The engulfment machinery is mainly required in circulating macrophages (hemocytes) after the discrimination between winners and losers is completed and the losers have been killed and extruded from the epithelium. Those new results leave us with the question as to which molecules allow winner cells to recognize and impose cell death on the loser cells during cell competition. During cell competition, winner cells induce apoptosis in loser cells by unknown mechanisms. Apoptotic debris is extruded basally from the epithelium to be cleared by hemocytes. © 2013 WILEY Periodicals, Inc.

Casas-Tinto S.,Spanish National Cancer Center | Casas-Tinto S.,Cajal Institute CSIC | Lolo F.-N.,Spanish National Cardiovascular Center | Lolo F.-N.,University of Bern | And 2 more authors.
Nature Communications | Year: 2015

Cell competition is a process by which the slow dividing cells (losers) are recognized and eliminated from growing tissues. Loser cells are extruded from the epithelium and engulfed by the haemocytes, the Drosophila macrophages. However, how macrophages identify the dying loser cells is unclear. Here we show that apoptotic loser cells secrete Tyrosyl-tRNA synthetase (TyrRS), which is best known as a core component of the translational machinery. Secreted TyrRS is cleaved by matrix metalloproteinases generating MiniTyr and EMAP fragments. EMAP acts as a guiding cue for macrophage migration in the Drosophila larvae, as it attracts the haemocytes to the apoptotic loser cells. JNK signalling and Kish, a component of the secretory pathway, are autonomously required for the active secretion of TyrRS by the loser cells. Altogether, this mechanism guarantees effective removal of unfit cells from the growing tissue.

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