Nuclear lamin stiffness is a barrier to 3D-migration, but softness can limit survival
| Autor: | Avathamsa Athirasala, Joe Swift, Jerome Irianto, Dennis E. Discher, Kyle R. Spinler, Rocky Diegmiller, Irena L. Ivanovska, Jae-Won Shin, Takamasa Harada, P.C. Dave P. Dingal |
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| Rok vydání: | 2014 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Cell Nucleus Shape Cell type animal structures Cell Survival Apoptosis Biology Article Cell Movement Cell Line Tumor medicine Humans Research Articles Cell Nucleus Gene knockdown integumentary system Lamin Type B Chemistry Mesenchymal stem cell Cell migration Cell Biology Cell sorting Lamin Type A Protein Structure Tertiary Cell biology medicine.anatomical_structure Gene Knockdown Techniques embryonic structures Immunology Nuclear lamina Nucleus Lamin |
| Zdroj: | The Journal of Cell Biology |
| Popis: | Lamins impede 3D migration but also promote survival against migration-induced stresses. Cell migration through solid tissue often involves large contortions of the nucleus, but biological significance is largely unclear. The nucleoskeletal protein lamin-A varies both within and between cell types and was shown here to contribute to cell sorting and survival in migration through constraining micropores. Lamin-A proved rate-limiting in 3D migration of diverse human cells that ranged from glioma and adenocarcinoma lines to primary mesenchymal stem cells (MSCs). Stoichiometry of A- to B-type lamins established an activation barrier, with high lamin-A:B producing extruded nuclear shapes after migration. Because the juxtaposed A and B polymer assemblies respectively conferred viscous and elastic stiffness to the nucleus, subpopulations with different A:B levels sorted in 3D migration. However, net migration was also biphasic in lamin-A, as wild-type lamin-A levels protected against stress-induced death, whereas deep knockdown caused broad defects in stress resistance. In vivo xenografts proved consistent with A:B-based cell sorting, and intermediate A:B-enhanced tumor growth. Lamins thus impede 3D migration but also promote survival against migration-induced stresses. |
| Databáze: | OpenAIRE |
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