Format

Send to

Choose Destination
Nat Commun. 2015 Apr 8;6:6619. doi: 10.1038/ncomms7619.

Interplay between chemotaxis and contact inhibition of locomotion determines exploratory cell migration.

Lin B1,2,3, Yin T4, Wu YI4, Inoue T1,2,5, Levchenko A1,3.

Author information

1
Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
2
Department of Cell Biology, Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
3
Department of Biomedical Engineering, Systems Biology Institute, Yale University, West Haven, Connecticut 06516, USA.
4
Department of Genetics and Developmental Biology, Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, Connecticut 06032, USA.
5
Precursory Research for Embryonic Science and Technology Investigator, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan.

Abstract

Directed cell migration in native environments is influenced by multiple migratory cues. These cues may include simultaneously occurring attractive soluble growth factor gradients and repulsive effects arising from cell-cell contact, termed contact inhibition of locomotion (CIL). How single cells reconcile potentially conflicting cues remains poorly understood. Here we show that a dynamic crosstalk between epidermal growth factor (EGF)-mediated chemotaxis and CIL guides metastatic breast cancer cell motility, whereby cells become progressively insensitive to CIL in a chemotactic input-dependent manner. This balance is determined via integration of protrusion-enhancing signalling from EGF gradients and protrusion-suppressing signalling induced by CIL, mediated in part through EphB. Our results further suggest that EphB and EGF signalling inputs control protrusion formation by converging onto regulation of phosphatidylinositol 3-kinase (PI3K). We propose that this intricate interplay may enhance the spread of loose cell ensembles in pathophysiological conditions such as cancer, and possibly other physiological settings.

PMID:
25851023
PMCID:
PMC4391292
DOI:
10.1038/ncomms7619
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center