title: Oncogenic transformation of Drosophila somatic cells induces a functional piRNA pathway.
abstract: Germline genes often become re-expressed in soma-derived human cancers as "cancer/testis antigens" (CTAs), and piRNA (PIWI-interacting RNA) pathway proteins are found among CTAs. However, whether and how the piRNA pathway contributes to oncogenesis in human neoplasms remain poorly understood. We found that oncogenic Ras combined with loss of the Hippo tumor suppressor pathway reactivates a primary piRNA pathway in Drosophila somatic cells coincident with oncogenic transformation. In these cells, Piwi becomes loaded with piRNAs derived from annotated generative loci, which are normally restricted to either the germline or the somatic follicle cells. Negating the pathway leads to increases in the expression of a wide variety of transposons and also altered expression of some protein-coding genes. This correlates with a reduction in the proliferation of the transformed cells in culture, suggesting that, at least in this context, the piRNA pathway may play a functional role in cancer.
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;
authors.forename: Delphine
authors.initials: D
authors.lastname: Fagegaltier
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, United Kingdom;
authors.forename: Ilaria
authors.initials: I
authors.lastname: Falciatori
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, United Kingdom;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Czech
authors.affiliation: The New York Genome Center, New York, New York 10011, USA;
authors.forename: Stephane
authors.initials: S
authors.lastname: Castel
authors.affiliation: Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
authors.affiliation: Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Simcox
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA; Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, United Kingdom; The New York Genome Center, New York, New York 10011, USA;
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D002478:Cells, Cultured; D004251:DNA Transposable Elements / Q000235:genetics; D004330:Drosophila / Q000166:cytology / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D010053:Ovary / Q000166:cytology; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D060565:Argonaute Proteins; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D034741:RNA, Small Interfering; C116498:piwi protein, Drosophila
keywords: Hippo; Piwi; Ras; Warts; piRNA; transposon