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HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis
Drosophila melanogaster has been a model for multiple human disease conditions, including cancer. Among Drosophila tissues, the eye development is particularly sensitive to perturbations of the embryonic signaling pathways, whose improper activation in humans underlies various forms of cancer. We ha...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713366/ https://www.ncbi.nlm.nih.gov/pubmed/33273532 http://dx.doi.org/10.1038/s41598-020-77942-x |
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author | Katanaev, Vladimir L. Kryuchkov, Mikhail Averkov, Volodymyr Savitsky, Mikhail Nikolaeva, Kseniya Klimova, Nadezhda Khaustov, Sergei Solis, Gonzalo P. |
author_facet | Katanaev, Vladimir L. Kryuchkov, Mikhail Averkov, Volodymyr Savitsky, Mikhail Nikolaeva, Kseniya Klimova, Nadezhda Khaustov, Sergei Solis, Gonzalo P. |
author_sort | Katanaev, Vladimir L. |
collection | PubMed |
description | Drosophila melanogaster has been a model for multiple human disease conditions, including cancer. Among Drosophila tissues, the eye development is particularly sensitive to perturbations of the embryonic signaling pathways, whose improper activation in humans underlies various forms of cancer. We have launched the HumanaFly project, whereas human genes expressed in breast cancer patients are screened for their ability to aberrate development of the Drosophila eye, hoping to thus identify novel oncogenes. Here we report identification of a breast cancer transgene, which upon expression in Drosophila produces eye malformation similar to the famous Glazed phenotype discovered by Thomas Morgan and decades later dissected to originate from mis-expression of Wingless (Wg). Wg is the ortholog of human Wnt proteins serving as ligands to initiate the developmental/oncogenic Wnt signaling pathway. Through genetic experiments we identified that this transgene interacted with the Wg production machinery, rather than with Wg signal transduction. In Drosophila imaginal discs, we directly show that the transgene promoted long-range diffusion of Wg, affecting expression of the Wg target genes. The transgene emerged to encode RPS12—a protein of the small ribosomal subunit overexpressed in several cancer types and known to also possess extra-ribosomal functions. Our work identifies RPS12 as an unexpected regulator of secretion and activity of Wnts. As Wnt signaling is particularly important in the context of breast cancer initiation and progression, RPS12 might be implicated in tumorigenesis in this and other Wnt-dependent cancers. Continuation of our HumanaFly project may bring further discoveries on oncogenic mechanisms. |
format | Online Article Text |
id | pubmed-7713366 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77133662020-12-03 HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis Katanaev, Vladimir L. Kryuchkov, Mikhail Averkov, Volodymyr Savitsky, Mikhail Nikolaeva, Kseniya Klimova, Nadezhda Khaustov, Sergei Solis, Gonzalo P. Sci Rep Article Drosophila melanogaster has been a model for multiple human disease conditions, including cancer. Among Drosophila tissues, the eye development is particularly sensitive to perturbations of the embryonic signaling pathways, whose improper activation in humans underlies various forms of cancer. We have launched the HumanaFly project, whereas human genes expressed in breast cancer patients are screened for their ability to aberrate development of the Drosophila eye, hoping to thus identify novel oncogenes. Here we report identification of a breast cancer transgene, which upon expression in Drosophila produces eye malformation similar to the famous Glazed phenotype discovered by Thomas Morgan and decades later dissected to originate from mis-expression of Wingless (Wg). Wg is the ortholog of human Wnt proteins serving as ligands to initiate the developmental/oncogenic Wnt signaling pathway. Through genetic experiments we identified that this transgene interacted with the Wg production machinery, rather than with Wg signal transduction. In Drosophila imaginal discs, we directly show that the transgene promoted long-range diffusion of Wg, affecting expression of the Wg target genes. The transgene emerged to encode RPS12—a protein of the small ribosomal subunit overexpressed in several cancer types and known to also possess extra-ribosomal functions. Our work identifies RPS12 as an unexpected regulator of secretion and activity of Wnts. As Wnt signaling is particularly important in the context of breast cancer initiation and progression, RPS12 might be implicated in tumorigenesis in this and other Wnt-dependent cancers. Continuation of our HumanaFly project may bring further discoveries on oncogenic mechanisms. Nature Publishing Group UK 2020-12-03 /pmc/articles/PMC7713366/ /pubmed/33273532 http://dx.doi.org/10.1038/s41598-020-77942-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Katanaev, Vladimir L. Kryuchkov, Mikhail Averkov, Volodymyr Savitsky, Mikhail Nikolaeva, Kseniya Klimova, Nadezhda Khaustov, Sergei Solis, Gonzalo P. HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis |
title | HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis |
title_full | HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis |
title_fullStr | HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis |
title_full_unstemmed | HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis |
title_short | HumanaFly: high-throughput transgenesis and expression of breast cancer transcripts in Drosophila eye discovers the RPS12-Wingless signaling axis |
title_sort | humanafly: high-throughput transgenesis and expression of breast cancer transcripts in drosophila eye discovers the rps12-wingless signaling axis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713366/ https://www.ncbi.nlm.nih.gov/pubmed/33273532 http://dx.doi.org/10.1038/s41598-020-77942-x |
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