Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival

J Cell Biol. 2014 Mar 3;204(5):669-82. doi: 10.1083/jcb.201308029. Epub 2014 Feb 24.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Cell Nucleus / ultrastructure
  • Cell Nucleus Shape
  • Cell Survival
  • Gene Knockdown Techniques
  • Humans
  • Lamin Type A / chemistry
  • Lamin Type A / genetics
  • Lamin Type A / physiology*
  • Lamin Type B / chemistry
  • Lamin Type B / genetics
  • Lamin Type B / physiology*
  • Protein Structure, Tertiary

Substances

  • Lamin Type A
  • Lamin Type B