title: JAK/STAT pathway dysregulation in tumors: a Drosophila perspective.
abstract: Sustained activation of the JAK/STAT pathway is causal to human cancers. This pathway is less complex in Drosophila, and its dysregulation has been linked to several tumor models in this organism. Here, we discuss models of metastatic epithelial and hematopoietic tumors that are causally linked to dysregulation of JAK/STAT signaling in Drosophila. First, we focus on cancer models in imaginal discs where ectopic expression of the JAK/STAT pathway ligand Unpaired downstream of distinct tumor suppressors has emerged as an unexpected mediator of neoplastic transformation. We also discuss the collaboration between STAT and oncogenic Ras in epithelial transformation. Second, we examine hematopoietic tumors, where mutations that cause hyperactive JAK/STAT signaling are necessary and sufficient for "fly leukemia". We highlight the important contributions that genetic screens in Drosophila have made to understanding the JAK/STAT pathway, its developmental roles, and how its function is co-opted during tumorigenesis.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 550 First Avenue, MSB 497B, New York, NY 10016, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Amoyel
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 550 First Avenue, MSB 497B, New York, NY 10016, USA.
authors.forename: Abigail M
authors.initials: AM
authors.lastname: Anderson
authors.affiliation: The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, New York University School of Medicine. Electronic address: erika.bach@nyu.edu.
authors.forename: Erika A
authors.initials: EA
authors.lastname: Bach
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D050791:STAT Transcription Factors; D014157:Transcription Factors; D053612:Janus Kinases; C085845:hop protein, Drosophila
keywords: Carcinoma; Chinmo; Dome; ESCRT; Hop; Imaginal discs; JAK/STAT; Melanotic tumors; Myeloproliferative neoplasms; Notch; PRC1; Ras; Scribbled; Socs36E; Stat92E; T42; Tum-l; Upd; dPIAS