title: Tumorigenic Properties of Drosophila Epithelial Cells Mutant for lethal giant larvae.
abstract: Mutations in Drosophila tumor suppressor genes (TSGs) lead to the formation of invasive tumors in the brain and imaginal discs.
  
  
  
  Here we studied the tumorigenic properties of imaginal discs mutant for the TSG gene lethal giant larvae (lgl). lgl mutant cells display the characteristic features of mammalian tumor cells: they can proliferate indefinitely, induce additional tracheogenesis (an insect counterpart of vasculogenesis) and invade neighboring tissues. Lgl mutant tissues exhibit high apoptotic levels, which lead to the activation of the Jun-N-Terminal Kinase (JNK) pathway. We propose that JNK is a key factor in the acquisition of these tumorigenic properties; it promotes cell proliferation and induces high levels of Mmp1 and confers tumor cells capacity to invade wild-type tissue. Noteworthy, lgl RNAi-mediated down-regulation does not produce similar transformations in the central nervous system (CNS), thereby indicating a fundamental difference between the cells of developing imaginal discs and those of differentiated organs. We discuss these results in the light of the "single big-hit origin" of some human pediatric or developmental cancers.
  
  
  
  Down-regulation of lgl in imaginal discs is sufficient to enhance tracheogenesis and to promote invasion and colonization of other larval structures including the CNS. Developmental Dynamics 245:834-843, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Centro de Biología Molecular, CSIC-UAM, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Calleja
authors.affiliation: Centro de Biología Molecular, CSIC-UAM, Madrid, Spain.
authors.forename: Ginés
authors.initials: G
authors.lastname: Morata
authors.affiliation: Institut de Biologia Molecular de Barcelona (CSIC) Barcelona, Catalonia, Spain.|Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Casanova
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D004330:Drosophila / Q000166:cytology* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000166:cytology* / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D025521:Tumor Suppressor Proteins; C081435:l(2)gl protein, Drosophila; D020781:Matrix Metalloproteinase 1
keywords: Drosophila tumors; JNK activity; apoptosis; lethal giant larvae; massive overgrowths; pediatric cancers; tracheogenesis and invasiveness