Angiogenesis

, Volume 11, Issue 1, pp 13–21

Slits and Roundabouts in cancer, tumour angiogenesis and endothelial cell migration

  • John A. Legg
  • John M. J. Herbert
  • Patricia Clissold
  • Roy Bicknell
Original Paper

DOI: 10.1007/s10456-008-9100-x

Cite this article as:
Legg, J.A., Herbert, J.M.J., Clissold, P. et al. Angiogenesis (2008) 11: 13. doi:10.1007/s10456-008-9100-x

Abstract

Angiogenesis describes the development of new blood vessels from pre-existing vessels. The hijacking of this physiological process by tumours allows them to develop their own supplies of nutrients and oxygen, enabling their growth and metastasis. A large body of literature has accumulated over the last 20 years relating to angiogenesis, including signalling pathways involved in this process. One such pathway uses Slit–Roundabout proteins that are implicated in the development of cancers and tumour angiogenesis. The Roundabout family of receptors are large, single-pass transmembrane cell surface receptors involved in directing cell migration in response to their cognate Slit ligands. Although best known for their role in neuronal development, Slits and Roundabouts have now been implicated in myogenesis, leukocyte chemotaxis and tumour angiogenesis, confirming that the Robo signalling pathway functions across multiple cell types. We review here the evidence for a role for Slits and Roundabouts in cancer. In particular, we focus on the role of Robo1 and Robo4 in tumour angiogenesis and discuss the signalling pathways downstream of these proteins mediating endothelial cell migration.

Keywords

Cell motilityEndotheliumGTPasesSignalling pathways

Abbreviations

Robo

Roundabouts

LRR

Leucine rich repeat

DUTT1

Deleted in U Twenty Twenty

Ig

Immunoglobulin-like

Fn

Fibronectin type III

CC

Cytoplasmic conserved

RoboN

Robo1 extracellular domain

GEF

Guanine nucleotide-exchange factor

GAP

GTPase activating protein

PAK

p21 Activated kinases

WASP

Wiskott–Aldrich syndrome protein

HUVEC

Human umbilical vein endothelial cells

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • John A. Legg
    • 1
  • John M. J. Herbert
    • 1
  • Patricia Clissold
    • 1
  • Roy Bicknell
    • 1
  1. 1.Cancer Research UK Angiogenesis Group, Institute for Biomedical ResearchUniversity of Birmingham Medical SchoolEdgbastonUK