AKT2-mediated nuclear deformation leads to genome instability during epithelial-mesenchymal transition
Summary: Nuclear deformation has been observed in some cancer cells for decades, but its underlying mechanism and biological significance remain elusive. To address these questions, we employed human lung cancer A549 cell line as a model in context with transforming growth factor β (TGFβ)-induced ep...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223010696 |
| _version_ | 1797808342048964608 |
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| author | Jia-Rong Fan Sung-Nian Chang Ching-Tung Chu Hong-Chen Chen |
| author_facet | Jia-Rong Fan Sung-Nian Chang Ching-Tung Chu Hong-Chen Chen |
| author_sort | Jia-Rong Fan |
| collection | DOAJ |
| description | Summary: Nuclear deformation has been observed in some cancer cells for decades, but its underlying mechanism and biological significance remain elusive. To address these questions, we employed human lung cancer A549 cell line as a model in context with transforming growth factor β (TGFβ)-induced epithelial-mesenchymal transition. Here, we report that nuclear deformation induced by TGFβ is concomitant with increased phosphorylation of lamin A at Ser390, defective nuclear lamina and genome instability. AKT2 and Smad3 serve as the downstream effectors for TGFβ to induce nuclear deformation. AKT2 directly phosphorylates lamin A at Ser390, whereas Smad3 is required for AKT2 activation upon TGFβ stimulation. Expression of the lamin A mutant with a substitution of Ser390 to Ala or suppression of AKT2 or Smad3 prevents nuclear deformation and genome instability induced by TGFβ. These findings reveal a molecular mechanism for TGFβ-induced nuclear deformation and establish a role of nuclear deformation in genome instability during epithelial-mesenchymal transition. |
| first_indexed | 2024-03-13T06:37:09Z |
| format | Article |
| id | doaj.art-85e028c55c9245099c6c9dd2a7d7fecc |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-13T06:37:09Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-85e028c55c9245099c6c9dd2a7d7fecc2023-06-09T04:28:55ZengElsevieriScience2589-00422023-06-01266106992AKT2-mediated nuclear deformation leads to genome instability during epithelial-mesenchymal transitionJia-Rong Fan0Sung-Nian Chang1Ching-Tung Chu2Hong-Chen Chen3Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei 11221, TaiwanInstitute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei 11221, TaiwanInstitute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei 11221, TaiwanInstitute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; Corresponding authorSummary: Nuclear deformation has been observed in some cancer cells for decades, but its underlying mechanism and biological significance remain elusive. To address these questions, we employed human lung cancer A549 cell line as a model in context with transforming growth factor β (TGFβ)-induced epithelial-mesenchymal transition. Here, we report that nuclear deformation induced by TGFβ is concomitant with increased phosphorylation of lamin A at Ser390, defective nuclear lamina and genome instability. AKT2 and Smad3 serve as the downstream effectors for TGFβ to induce nuclear deformation. AKT2 directly phosphorylates lamin A at Ser390, whereas Smad3 is required for AKT2 activation upon TGFβ stimulation. Expression of the lamin A mutant with a substitution of Ser390 to Ala or suppression of AKT2 or Smad3 prevents nuclear deformation and genome instability induced by TGFβ. These findings reveal a molecular mechanism for TGFβ-induced nuclear deformation and establish a role of nuclear deformation in genome instability during epithelial-mesenchymal transition.http://www.sciencedirect.com/science/article/pii/S2589004223010696Cell biology |
| spellingShingle | Jia-Rong Fan Sung-Nian Chang Ching-Tung Chu Hong-Chen Chen AKT2-mediated nuclear deformation leads to genome instability during epithelial-mesenchymal transition iScience Cell biology |
| title | AKT2-mediated nuclear deformation leads to genome instability during epithelial-mesenchymal transition |
| title_full | AKT2-mediated nuclear deformation leads to genome instability during epithelial-mesenchymal transition |
| title_fullStr | AKT2-mediated nuclear deformation leads to genome instability during epithelial-mesenchymal transition |
| title_full_unstemmed | AKT2-mediated nuclear deformation leads to genome instability during epithelial-mesenchymal transition |
| title_short | AKT2-mediated nuclear deformation leads to genome instability during epithelial-mesenchymal transition |
| title_sort | akt2 mediated nuclear deformation leads to genome instability during epithelial mesenchymal transition |
| topic | Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223010696 |
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