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Evidence for a novel function of Awd in maintenance of genomic stability
The abnormal wing discs (awd) gene encodes the Drosophila homolog of NME1/NME2 metastasis suppressor genes. Awd acts in multiple tissues where its function is critical in establishing and maintaining epithelial integrity. Here, we analysed awd gene function in Drosophila epithelial cells using trans...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714947/ https://www.ncbi.nlm.nih.gov/pubmed/29203880 http://dx.doi.org/10.1038/s41598-017-17217-0 |
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author | Romani, Patrizia Duchi, Serena Gargiulo, Giuseppe Cavaliere, Valeria |
author_facet | Romani, Patrizia Duchi, Serena Gargiulo, Giuseppe Cavaliere, Valeria |
author_sort | Romani, Patrizia |
collection | PubMed |
description | The abnormal wing discs (awd) gene encodes the Drosophila homolog of NME1/NME2 metastasis suppressor genes. Awd acts in multiple tissues where its function is critical in establishing and maintaining epithelial integrity. Here, we analysed awd gene function in Drosophila epithelial cells using transgene-mediated RNA interference and genetic mosaic analysis. We show that awd knockdown in larval wing disc epithelium leads to chromosomal instability (CIN) and induces apoptosis mediated by activation of c-Jun N-terminal kinase. Forced maintenance of Awd depleted cells, by expressing the cell death inhibitor p35, downregulates atypical protein kinase C and DE-Cadherin. Consistent with their loss of cell polarity and enhanced level of matrix metalloproteinase 1, cells delaminate from wing disc epithelium. Furthermore, the DNA content profile of these cells indicates that they are aneuploid. Overall, our data demonstrate a novel function for awd in maintenance of genomic stability. Our results are consistent with other studies reporting that NME1 down-regulation induces CIN in human cell lines and suggest that Drosophila model could be successfully used to study in vivo the impact of NME/Awd - induced genomic instability on tumour development and metastasis formation. |
format | Online Article Text |
id | pubmed-5714947 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57149472017-12-08 Evidence for a novel function of Awd in maintenance of genomic stability Romani, Patrizia Duchi, Serena Gargiulo, Giuseppe Cavaliere, Valeria Sci Rep Article The abnormal wing discs (awd) gene encodes the Drosophila homolog of NME1/NME2 metastasis suppressor genes. Awd acts in multiple tissues where its function is critical in establishing and maintaining epithelial integrity. Here, we analysed awd gene function in Drosophila epithelial cells using transgene-mediated RNA interference and genetic mosaic analysis. We show that awd knockdown in larval wing disc epithelium leads to chromosomal instability (CIN) and induces apoptosis mediated by activation of c-Jun N-terminal kinase. Forced maintenance of Awd depleted cells, by expressing the cell death inhibitor p35, downregulates atypical protein kinase C and DE-Cadherin. Consistent with their loss of cell polarity and enhanced level of matrix metalloproteinase 1, cells delaminate from wing disc epithelium. Furthermore, the DNA content profile of these cells indicates that they are aneuploid. Overall, our data demonstrate a novel function for awd in maintenance of genomic stability. Our results are consistent with other studies reporting that NME1 down-regulation induces CIN in human cell lines and suggest that Drosophila model could be successfully used to study in vivo the impact of NME/Awd - induced genomic instability on tumour development and metastasis formation. Nature Publishing Group UK 2017-12-04 /pmc/articles/PMC5714947/ /pubmed/29203880 http://dx.doi.org/10.1038/s41598-017-17217-0 Text en © The Author(s) 2017 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Romani, Patrizia Duchi, Serena Gargiulo, Giuseppe Cavaliere, Valeria Evidence for a novel function of Awd in maintenance of genomic stability |
title | Evidence for a novel function of Awd in maintenance of genomic stability |
title_full | Evidence for a novel function of Awd in maintenance of genomic stability |
title_fullStr | Evidence for a novel function of Awd in maintenance of genomic stability |
title_full_unstemmed | Evidence for a novel function of Awd in maintenance of genomic stability |
title_short | Evidence for a novel function of Awd in maintenance of genomic stability |
title_sort | evidence for a novel function of awd in maintenance of genomic stability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714947/ https://www.ncbi.nlm.nih.gov/pubmed/29203880 http://dx.doi.org/10.1038/s41598-017-17217-0 |
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