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Tumorigenic Properties of Drosophila Epithelial Cells Mutant for lethal giant larvae
Author(s) -
Calleja Manuel,
Morata Ginés,
Casanova Jordi
Publication year - 2016
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24420
Subject(s) - imaginal disc , biology , microbiology and biotechnology , mutant , suppressor , rna interference , gene , cancer research , genetics , rna
Background: Mutations in Drosophila tumor suppressor genes (TSGs) lead to the formation of invasive tumors in the brain and imaginal discs. Results: 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. Conclusions: 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.