Abstract |
Collective cell migration occurs in a range of contexts: cancer cells frequently invade in cohorts while retaining cell-cell junctions. Here we show that collective invasion by cancer cells depends on decreasing actomyosin contractility at sites of cell-cell contact. When actomyosin is not downregulated at cell-cell contacts, migrating cells lose cohesion. We provide a molecular mechanism for this downregulation. Depletion of discoidin domain receptor 1 (DDR1) blocks collective cancer-cell invasion in a range of two-dimensional, three-dimensional and 'organotypic' models. DDR1 coordinates the Par3/Par6 cell-polarity complex through its carboxy terminus, binding PDZ domains in Par3 and Par6. The DDR1-Par3/Par6 complex controls the localization of RhoE to cell-cell contacts, where it antagonizes ROCK-driven actomyosin contractility. Depletion of DDR1, Par3, Par6 or RhoE leads to increased actomyosin contactility at cell-cell contacts, a loss of cell-cell cohesion and defective collective cell invasion.
|
Authors | Cristina Hidalgo-Carcedo, Steven Hooper, Shahid I Chaudhry, Peter Williamson, Kevin Harrington, Birgit Leitinger, Erik Sahai |
Journal | Nature cell biology
(Nat Cell Biol)
Vol. 13
Issue 1
Pg. 49-58
(Jan 2011)
ISSN: 1476-4679 [Electronic] England |
PMID | 21170030
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Adaptor Proteins, Signal Transducing
- Cell Cycle Proteins
- Membrane Proteins
- PARD3 protein, human
- PARD6A protein, human
- Green Fluorescent Proteins
- Actomyosin
- DDR1 protein, human
- Discoidin Domain Receptor 1
- Receptor Protein-Tyrosine Kinases
- RND3 protein, human
- rho GTP-Binding Proteins
|
Topics |
- Actomyosin
(metabolism)
- Adaptor Proteins, Signal Transducing
(genetics, metabolism)
- Amino Acid Sequence
- Blotting, Western
- Cell Adhesion
- Cell Communication
- Cell Cycle Proteins
(genetics, metabolism)
- Cell Line
- Cell Line, Tumor
- Cell Movement
- Cell Polarity
- Discoidin Domain Receptor 1
- Green Fluorescent Proteins
(genetics, metabolism)
- Humans
- Membrane Proteins
(genetics, metabolism)
- Microscopy, Fluorescence
- Protein Binding
- RNA Interference
- Receptor Protein-Tyrosine Kinases
(genetics, metabolism)
- Sequence Homology, Amino Acid
- Tight Junctions
(metabolism)
- rho GTP-Binding Proteins
(genetics, metabolism)
|