A tumor-suppressing mechanism in Drosophila involving cell competition and the Hippo pathway.
Mutant larvae for the Drosophila gene lethal giant larva (lgl) develop neoplastic tumors in imaginal discs. However, lgl mutant clones do not form tumors when surrounded by wild-type tissue, suggesting the existence of a tumor-suppressing mechanism. We have investigated the tumorigenic potential of lgl mutant cells by generating wing compartments that are entirely mutant for lgl and also inducing clones of various genetic combinations of lgl(-) cells. We find that lgl(-) compartments can grow indefinitely but lgl(-) clones are eliminated by cell competition. lgl mutant cells may form tumors if they acquire constitutive activity of the Ras pathway (lgl(-) UAS-ras(V12)), which confers proliferation advantage through inhibition of the Hippo pathway. Yet, the majority of lgl(-) UAS-ras(V12) clones are eliminated in spite of their high proliferation rate. The formation of a tumor requires in addition the formation of a microenvironment that allows mutant cells to evade cell competition.
Menéndez
Javier
J
Centro de Biología Molecular, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid 28049, Spain.
Pérez-Garijo
Ainhoa
A
Calleja
Manuel
M
Morata
Ginés
G
D000818:Animals; D002450:Cell Communication; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014921:Wings, Animal / Q000166:cytology / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism; D000099317:Hippo Kinases
D029721:Drosophila Proteins; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; D018631:ras Proteins; C081435:l(2)gl protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases