Vav1 Selectively Down-Regulates Akt2 through miR-29b in Certain Breast Tumors with Triple Negative Phenotype
Triple negative breast cancer (TNBC) represents the most aggressive breast tumor, showing a high intrinsic variability in terms of both histopathological features and response to therapies. Blocking the Akt signaling pathway is a well-studied approach in the treatment of aggressive breast tumors. Th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/6/993 |
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| author | Silvia Grassilli Federica Brugnoli Stefano Cairo Nicoletta Bianchi Jean-Gabriel Judde Valeria Bertagnolo |
| author_facet | Silvia Grassilli Federica Brugnoli Stefano Cairo Nicoletta Bianchi Jean-Gabriel Judde Valeria Bertagnolo |
| author_sort | Silvia Grassilli |
| collection | DOAJ |
| description | Triple negative breast cancer (TNBC) represents the most aggressive breast tumor, showing a high intrinsic variability in terms of both histopathological features and response to therapies. Blocking the Akt signaling pathway is a well-studied approach in the treatment of aggressive breast tumors. The high homology among the Akt isoforms and their distinct, and possibly opposite, oncogenic functions made it difficult to develop effective drugs. Here we investigated the role of Vav1 as a potential down-regulator of individual Akt isozymes. We revealed that the over-expression of Vav1 in triple negative MDA-MB-231 cells reduced only the Akt2 isoform, acting at the post-transcriptional level through the up-modulation of miR-29b. The Vav1/miR-29b dependent decrease in Akt2 was correlated with a reduced lung colonization of circulating MDA-MB-231 cells. In cell lines established from PDX, the Vav1 induced down-modulation of Akt2 is strongly dependent on miR-29b and occurs only in some TNBC tumors. These findings may contribute to better classify breast tumors having the triple negative phenotype, and suggest that the activation of the Vav1/miR-29b axis, precisely regulating the amount of an Akt isozyme crucial for tumor dissemination, could have great potential for driving more accurate therapies to TNBCs, often not eligible or resistant to treatments. |
| first_indexed | 2024-03-09T23:20:03Z |
| format | Article |
| id | doaj.art-f94c872ce3304310bde04efa4f3dfdd7 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-09T23:20:03Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-f94c872ce3304310bde04efa4f3dfdd72023-11-23T17:28:54ZengMDPI AGJournal of Personalized Medicine2075-44262022-06-0112699310.3390/jpm12060993Vav1 Selectively Down-Regulates Akt2 through miR-29b in Certain Breast Tumors with Triple Negative PhenotypeSilvia Grassilli0Federica Brugnoli1Stefano Cairo2Nicoletta Bianchi3Jean-Gabriel Judde4Valeria Bertagnolo5Department of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyXentech, 91000 Evry, FranceDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyXentech, 91000 Evry, FranceDepartment of Translational Medicine, University of Ferrara, 44121 Ferrara, ItalyTriple negative breast cancer (TNBC) represents the most aggressive breast tumor, showing a high intrinsic variability in terms of both histopathological features and response to therapies. Blocking the Akt signaling pathway is a well-studied approach in the treatment of aggressive breast tumors. The high homology among the Akt isoforms and their distinct, and possibly opposite, oncogenic functions made it difficult to develop effective drugs. Here we investigated the role of Vav1 as a potential down-regulator of individual Akt isozymes. We revealed that the over-expression of Vav1 in triple negative MDA-MB-231 cells reduced only the Akt2 isoform, acting at the post-transcriptional level through the up-modulation of miR-29b. The Vav1/miR-29b dependent decrease in Akt2 was correlated with a reduced lung colonization of circulating MDA-MB-231 cells. In cell lines established from PDX, the Vav1 induced down-modulation of Akt2 is strongly dependent on miR-29b and occurs only in some TNBC tumors. These findings may contribute to better classify breast tumors having the triple negative phenotype, and suggest that the activation of the Vav1/miR-29b axis, precisely regulating the amount of an Akt isozyme crucial for tumor dissemination, could have great potential for driving more accurate therapies to TNBCs, often not eligible or resistant to treatments.https://www.mdpi.com/2075-4426/12/6/993triple negative breast cancer (TNBC)miR-29bVav1Akt2targeted therapy |
| spellingShingle | Silvia Grassilli Federica Brugnoli Stefano Cairo Nicoletta Bianchi Jean-Gabriel Judde Valeria Bertagnolo Vav1 Selectively Down-Regulates Akt2 through miR-29b in Certain Breast Tumors with Triple Negative Phenotype Journal of Personalized Medicine triple negative breast cancer (TNBC) miR-29b Vav1 Akt2 targeted therapy |
| title | Vav1 Selectively Down-Regulates Akt2 through miR-29b in Certain Breast Tumors with Triple Negative Phenotype |
| title_full | Vav1 Selectively Down-Regulates Akt2 through miR-29b in Certain Breast Tumors with Triple Negative Phenotype |
| title_fullStr | Vav1 Selectively Down-Regulates Akt2 through miR-29b in Certain Breast Tumors with Triple Negative Phenotype |
| title_full_unstemmed | Vav1 Selectively Down-Regulates Akt2 through miR-29b in Certain Breast Tumors with Triple Negative Phenotype |
| title_short | Vav1 Selectively Down-Regulates Akt2 through miR-29b in Certain Breast Tumors with Triple Negative Phenotype |
| title_sort | vav1 selectively down regulates akt2 through mir 29b in certain breast tumors with triple negative phenotype |
| topic | triple negative breast cancer (TNBC) miR-29b Vav1 Akt2 targeted therapy |
| url | https://www.mdpi.com/2075-4426/12/6/993 |
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