دورية أكاديمية
Lamin A and the LINC complex act as potential tumor suppressors in Ewing Sarcoma
| العنوان: | Lamin A and the LINC complex act as potential tumor suppressors in Ewing Sarcoma |
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| المؤلفون: | Francesca Chiarini, Francesca Paganelli, Tommaso Balestra, Cristina Capanni, Antonietta Fazio, Maria Cristina Manara, Lorena Landuzzi, Stefania Petrini, Camilla Evangelisti, Pier-Luigi Lollini, Alberto M. Martelli, Giovanna Lattanzi, Katia Scotlandi |
| المصدر: | Cell Death and Disease, Vol 13, Iss 4, Pp 1-13 (2022) |
| بيانات النشر: | Nature Publishing Group, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Cytology |
| مصطلحات موضوعية: | Cytology, QH573-671 |
| الوصف: | Abstract Lamin A, a main constituent of the nuclear lamina, is involved in mechanosignaling and cell migration through dynamic interactions with the LINC complex, formed by the nuclear envelope proteins SUN1, SUN2 and the nesprins. Here, we investigated lamin A role in Ewing Sarcoma (EWS), an aggressive bone tumor affecting children and young adults. In patients affected by EWS, we found a significant inverse correlation between LMNA gene expression and tumor aggressiveness. Accordingly, in experimental in vitro models, low lamin A expression correlated with enhanced cell migration and invasiveness and, in vivo, with an increased metastatic load. At the molecular level, this condition was linked to altered expression and anchorage of nuclear envelope proteins and increased nuclear retention of YAP/TAZ, a mechanosignaling effector. Conversely, overexpression of lamin A rescued LINC complex organization, thus reducing YAP/TAZ nuclear recruitment and preventing cell invasiveness. These effects were also obtained through modulation of lamin A maturation by a statin-based pharmacological treatment that further elicited a more differentiated phenotype in EWS cells. These results demonstrate that drugs inducing nuclear envelope remodeling could be exploited to improve therapeutic strategies for EWS. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2041-4889 64786927 |
| العلاقة: | https://doaj.org/toc/2041-4889Test |
| DOI: | 10.1038/s41419-022-04729-5 |
| الوصول الحر: | https://doaj.org/article/5d5b516d43e64786927cb4086677f8b3Test |
| رقم الانضمام: | edsdoj.5d5b516d43e64786927cb4086677f8b3 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20414889 64786927 |
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| DOI: | 10.1038/s41419-022-04729-5 |