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Oncogenic transformation of Drosophila somatic cells induces a functional piRNA pathway

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 fou...

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Autores principales: Fagegaltier, Delphine, Falciatori, Ilaria, Czech, Benjamin, Castel, Stephane, Perrimon, Norbert, Simcox, Amanda, Hannon, Gregory J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973292/
https://www.ncbi.nlm.nih.gov/pubmed/27474441
http://dx.doi.org/10.1101/gad.284927.116
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author Fagegaltier, Delphine
Falciatori, Ilaria
Czech, Benjamin
Castel, Stephane
Perrimon, Norbert
Simcox, Amanda
Hannon, Gregory J.
author_facet Fagegaltier, Delphine
Falciatori, Ilaria
Czech, Benjamin
Castel, Stephane
Perrimon, Norbert
Simcox, Amanda
Hannon, Gregory J.
author_sort Fagegaltier, Delphine
collection PubMed
description 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.
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spelling pubmed-49732922017-01-15 Oncogenic transformation of Drosophila somatic cells induces a functional piRNA pathway Fagegaltier, Delphine Falciatori, Ilaria Czech, Benjamin Castel, Stephane Perrimon, Norbert Simcox, Amanda Hannon, Gregory J. Genes Dev Research Paper 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. Cold Spring Harbor Laboratory Press 2016-07-15 /pmc/articles/PMC4973292/ /pubmed/27474441 http://dx.doi.org/10.1101/gad.284927.116 Text en © 2016 Fagegaltier et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Fagegaltier, Delphine
Falciatori, Ilaria
Czech, Benjamin
Castel, Stephane
Perrimon, Norbert
Simcox, Amanda
Hannon, Gregory J.
Oncogenic transformation of Drosophila somatic cells induces a functional piRNA pathway
title Oncogenic transformation of Drosophila somatic cells induces a functional piRNA pathway
title_full Oncogenic transformation of Drosophila somatic cells induces a functional piRNA pathway
title_fullStr Oncogenic transformation of Drosophila somatic cells induces a functional piRNA pathway
title_full_unstemmed Oncogenic transformation of Drosophila somatic cells induces a functional piRNA pathway
title_short Oncogenic transformation of Drosophila somatic cells induces a functional piRNA pathway
title_sort oncogenic transformation of drosophila somatic cells induces a functional pirna pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973292/
https://www.ncbi.nlm.nih.gov/pubmed/27474441
http://dx.doi.org/10.1101/gad.284927.116
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