| Autor: |
Karina D. Rysenkova, Julia Gaboriaud, Artem I. Fokin, Raphaëlle Toubiana, Alexandre Bense, Camil Mirdass, Mélissa Jin, Minh Chau N. Ho, Elizabeth Glading, Sophie Vacher, Laura Courtois, Ivan Bièche, Alexis M. Gautreau |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cells, Vol 13, Iss 10, p 876 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2073-4409 |
| DOI: |
10.3390/cells13100876 |
| Popis: |
Breast cancer develops upon sequential acquisition of driver mutations in mammary epithelial cells; however, how these mutations collaborate to transform normal cells remains unclear in most cases. We aimed to reconstitute this process in a particular case. To this end, we combined the activated form of the PI 3-kinase harboring the H1047R mutation with the inactivation of the histone lysine methyl-transferase KMT2D in the non-tumorigenic human mammary epithelial cell line MCF10A. We found that PI 3-kinase activation promoted cell-cycle progression, especially when growth signals were limiting, as well as cell migration, both in a collective monolayer and as single cells. Furthermore, we showed that KMT2D inactivation had relatively little influence on these processes, except for single-cell migration, which KMT2D inactivation promoted in synergy with PI 3-kinase activation. The combination of these two genetic alterations induced expression of the ARPC5L gene that encodes a subunit of the Arp2/3 complex. ARPC5L depletion fully abolished the enhanced migration persistence exhibited by double-mutant cells. Our reconstitution approach in MCF10A has thus revealed both the cell function and the single-cell migration, and the underlying Arp2/3-dependent mechanism, which are synergistically regulated when KMT2D inactivation is combined with the activation of the PI 3-kinase. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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