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

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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.

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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

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Correspondence to Roy Bicknell.

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Legg, J.A., Herbert, J.M.J., Clissold, P. et al. Slits and Roundabouts in cancer, tumour angiogenesis and endothelial cell migration. Angiogenesis 11, 13–21 (2008). https://doi.org/10.1007/s10456-008-9100-x

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  • DOI: https://doi.org/10.1007/s10456-008-9100-x

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