<i>Drosophila</i> as Model System to Study Ras-Mediated Oncogenesis: The Case of the Tensin Family of Proteins
Oncogenic mutations in the small GTPase Ras contribute to ~30% of human cancers. However, tissue growth induced by oncogenic Ras is restrained by the induction of cellular senescence, and additional mutations are required to induce tumor progression. Therefore, identifying cooperating cancer genes i...
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MDPI AG
2023-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/7/1502 |
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| author | Ana Martínez-Abarca Millán Jennifer Soler Beatty Andrea Valencia Expósito María D. Martín-Bermudo |
| author_facet | Ana Martínez-Abarca Millán Jennifer Soler Beatty Andrea Valencia Expósito María D. Martín-Bermudo |
| author_sort | Ana Martínez-Abarca Millán |
| collection | DOAJ |
| description | Oncogenic mutations in the small GTPase Ras contribute to ~30% of human cancers. However, tissue growth induced by oncogenic Ras is restrained by the induction of cellular senescence, and additional mutations are required to induce tumor progression. Therefore, identifying cooperating cancer genes is of paramount importance. Recently, the tensin family of focal adhesion proteins, TNS1-4, have emerged as regulators of carcinogenesis, yet their role in cancer appears somewhat controversial. Around 90% of human cancers are of epithelial origin. We have used the <i>Drosophila</i> wing imaginal disc epithelium as a model system to gain insight into the roles of two orthologs of human TNS2 and 4, <i>blistery</i> (<i>by</i>) and <i>PVRAP</i>, in epithelial cancer progression. We have generated null mutations in <i>PVRAP</i> and found that, as is the case for <i>by</i> and mammalian tensins, <i>PVRAP</i> mutants are viable. We have also found that elimination of either <i>PVRAP</i> or <i>by</i> potentiates <i>Ras<sup>V12</sup></i>-mediated wing disc hyperplasia. Furthermore, our results have unraveled a mechanism by which tensins may limit Ras oncogenic capacity, the regulation of cell shape and growth. These results demonstrate that <i>Drosophila</i> tensins behave as suppressors of Ras-driven tissue hyperplasia, suggesting that the roles of tensins as modulators of cancer progression might be evolutionarily conserved. |
| first_indexed | 2024-03-11T01:03:03Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T01:03:03Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-ba1826c8e6ac4e9cad642498ff50f4c12023-11-18T19:31:30ZengMDPI AGGenes2073-44252023-07-01147150210.3390/genes14071502<i>Drosophila</i> as Model System to Study Ras-Mediated Oncogenesis: The Case of the Tensin Family of ProteinsAna Martínez-Abarca Millán0Jennifer Soler Beatty1Andrea Valencia Expósito2María D. Martín-Bermudo3Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide/CSIC/JA, Ctra Utrera Km1, 41013 Sevilla, SpainCentro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide/CSIC/JA, Ctra Utrera Km1, 41013 Sevilla, SpainCentro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide/CSIC/JA, Ctra Utrera Km1, 41013 Sevilla, SpainCentro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide/CSIC/JA, Ctra Utrera Km1, 41013 Sevilla, SpainOncogenic mutations in the small GTPase Ras contribute to ~30% of human cancers. However, tissue growth induced by oncogenic Ras is restrained by the induction of cellular senescence, and additional mutations are required to induce tumor progression. Therefore, identifying cooperating cancer genes is of paramount importance. Recently, the tensin family of focal adhesion proteins, TNS1-4, have emerged as regulators of carcinogenesis, yet their role in cancer appears somewhat controversial. Around 90% of human cancers are of epithelial origin. We have used the <i>Drosophila</i> wing imaginal disc epithelium as a model system to gain insight into the roles of two orthologs of human TNS2 and 4, <i>blistery</i> (<i>by</i>) and <i>PVRAP</i>, in epithelial cancer progression. We have generated null mutations in <i>PVRAP</i> and found that, as is the case for <i>by</i> and mammalian tensins, <i>PVRAP</i> mutants are viable. We have also found that elimination of either <i>PVRAP</i> or <i>by</i> potentiates <i>Ras<sup>V12</sup></i>-mediated wing disc hyperplasia. Furthermore, our results have unraveled a mechanism by which tensins may limit Ras oncogenic capacity, the regulation of cell shape and growth. These results demonstrate that <i>Drosophila</i> tensins behave as suppressors of Ras-driven tissue hyperplasia, suggesting that the roles of tensins as modulators of cancer progression might be evolutionarily conserved.https://www.mdpi.com/2073-4425/14/7/1502oncogenic Rasovergrowthtensins<i>Drosophila</i> |
| spellingShingle | Ana Martínez-Abarca Millán Jennifer Soler Beatty Andrea Valencia Expósito María D. Martín-Bermudo <i>Drosophila</i> as Model System to Study Ras-Mediated Oncogenesis: The Case of the Tensin Family of Proteins Genes oncogenic Ras overgrowth tensins <i>Drosophila</i> |
| title | <i>Drosophila</i> as Model System to Study Ras-Mediated Oncogenesis: The Case of the Tensin Family of Proteins |
| title_full | <i>Drosophila</i> as Model System to Study Ras-Mediated Oncogenesis: The Case of the Tensin Family of Proteins |
| title_fullStr | <i>Drosophila</i> as Model System to Study Ras-Mediated Oncogenesis: The Case of the Tensin Family of Proteins |
| title_full_unstemmed | <i>Drosophila</i> as Model System to Study Ras-Mediated Oncogenesis: The Case of the Tensin Family of Proteins |
| title_short | <i>Drosophila</i> as Model System to Study Ras-Mediated Oncogenesis: The Case of the Tensin Family of Proteins |
| title_sort | i drosophila i as model system to study ras mediated oncogenesis the case of the tensin family of proteins |
| topic | oncogenic Ras overgrowth tensins <i>Drosophila</i> |
| url | https://www.mdpi.com/2073-4425/14/7/1502 |
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