Nuclear Actin Polymerization Regulates Cell Epithelial‐Mesenchymal Transition
Abstract Current studies on actin function primarily rely on cytoplasmic actin due to the absence of cellular models specifically expressing nuclear actin. Here, cell models capable of expressing varying levels of nuclear F/G‐actin are generated and a significant role of nuclear actin in the regulat...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202300425 |
| _version_ | 1797663901705306112 |
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| author | William W. Du Javeria Qadir Kevin Y. Du Yu Chen Nan Wu Burton B. Yang |
| author_facet | William W. Du Javeria Qadir Kevin Y. Du Yu Chen Nan Wu Burton B. Yang |
| author_sort | William W. Du |
| collection | DOAJ |
| description | Abstract Current studies on actin function primarily rely on cytoplasmic actin due to the absence of cellular models specifically expressing nuclear actin. Here, cell models capable of expressing varying levels of nuclear F/G‐actin are generated and a significant role of nuclear actin in the regulation of epithelial‐mesenchymal transition (EMT) is uncovered. Through immunoprecipitation and mass spectrometry analyses, distinct binding partners for nuclear F‐actin (β‐catenin, SMAD2, and SMAD3) and nuclear G‐actin (MYBBP1A, NKRF, and MYPOP) are investigated, which respectively modulate EMT‐promoting and EMT‐repressing transcriptional events. While nuclear F‐actin promotes EMT with enhanced cell migration, survival, and elongated mesenchymal morphology, nuclear G‐actin represses EMT and related cell activities. Mechanistically, nuclear F‐actin enhances β‐catenin, SMAD2, and SMAD3 expression and stability in the nuclei, while nuclear G‐actin increases MYBBP1A, NKRF, and MYPOP expression and stability in the nuclei. The association between nuclear F/G‐actin and N‐cadherin/E‐cadherin in the cell lines (in vitro), and increased nuclear actin polymerization in the wound healing cells (in vivo) affirm a significant role of nuclear actin in EMT regulation. With evidence of nuclear actin polymerization and EMT during development, and irregularities in disease states such as cancer and fibrosis, targeting nuclear actin dynamics to trigger dysregulated EMT warrants ongoing study. |
| first_indexed | 2024-03-11T19:22:28Z |
| format | Article |
| id | doaj.art-cc9bd908e2e74f49ac6bc8c39f7a138d |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-11T19:22:28Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-cc9bd908e2e74f49ac6bc8c39f7a138d2023-10-07T03:51:50ZengWileyAdvanced Science2198-38442023-10-011028n/an/a10.1002/advs.202300425Nuclear Actin Polymerization Regulates Cell Epithelial‐Mesenchymal TransitionWilliam W. Du0Javeria Qadir1Kevin Y. Du2Yu Chen3Nan Wu4Burton B. Yang5Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON M4N3M5 CanadaSunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON M4N3M5 CanadaSunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON M4N3M5 CanadaSunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON M4N3M5 CanadaSunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON M4N3M5 CanadaSunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON M4N3M5 CanadaAbstract Current studies on actin function primarily rely on cytoplasmic actin due to the absence of cellular models specifically expressing nuclear actin. Here, cell models capable of expressing varying levels of nuclear F/G‐actin are generated and a significant role of nuclear actin in the regulation of epithelial‐mesenchymal transition (EMT) is uncovered. Through immunoprecipitation and mass spectrometry analyses, distinct binding partners for nuclear F‐actin (β‐catenin, SMAD2, and SMAD3) and nuclear G‐actin (MYBBP1A, NKRF, and MYPOP) are investigated, which respectively modulate EMT‐promoting and EMT‐repressing transcriptional events. While nuclear F‐actin promotes EMT with enhanced cell migration, survival, and elongated mesenchymal morphology, nuclear G‐actin represses EMT and related cell activities. Mechanistically, nuclear F‐actin enhances β‐catenin, SMAD2, and SMAD3 expression and stability in the nuclei, while nuclear G‐actin increases MYBBP1A, NKRF, and MYPOP expression and stability in the nuclei. The association between nuclear F/G‐actin and N‐cadherin/E‐cadherin in the cell lines (in vitro), and increased nuclear actin polymerization in the wound healing cells (in vivo) affirm a significant role of nuclear actin in EMT regulation. With evidence of nuclear actin polymerization and EMT during development, and irregularities in disease states such as cancer and fibrosis, targeting nuclear actin dynamics to trigger dysregulated EMT warrants ongoing study.https://doi.org/10.1002/advs.202300425actin polymerizationepithelial‐mesenchymal transitionnuclear actintranscription factorwound healing |
| spellingShingle | William W. Du Javeria Qadir Kevin Y. Du Yu Chen Nan Wu Burton B. Yang Nuclear Actin Polymerization Regulates Cell Epithelial‐Mesenchymal Transition Advanced Science actin polymerization epithelial‐mesenchymal transition nuclear actin transcription factor wound healing |
| title | Nuclear Actin Polymerization Regulates Cell Epithelial‐Mesenchymal Transition |
| title_full | Nuclear Actin Polymerization Regulates Cell Epithelial‐Mesenchymal Transition |
| title_fullStr | Nuclear Actin Polymerization Regulates Cell Epithelial‐Mesenchymal Transition |
| title_full_unstemmed | Nuclear Actin Polymerization Regulates Cell Epithelial‐Mesenchymal Transition |
| title_short | Nuclear Actin Polymerization Regulates Cell Epithelial‐Mesenchymal Transition |
| title_sort | nuclear actin polymerization regulates cell epithelial mesenchymal transition |
| topic | actin polymerization epithelial‐mesenchymal transition nuclear actin transcription factor wound healing |
| url | https://doi.org/10.1002/advs.202300425 |
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