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

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.

Molecular discrimination of cutaneous squamous cell carcinoma from actinic keratosis and normal skin

“…15,16 Although COL6A3 has not been associated with tumorigenesis, alterations of extracellular matrix-binding proteins would seem necessary for progression and invasion of the dermis by squamous cell carcinoma. The downregulated genes CASZ1, RTN4 (Nogo-A), and NFIB also have been associated with tumorigenesis.…”

Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: Clinical and prognostic implications

“…ROBO3 and ROBO4 are receptors of SLIT and are involved in neuronal axis formation, angiogenesis, etc. 20, 21 Narayan et al 22 reported methylation (36%) of ROBO3 in CACX with no detectable expression of ROBO3 in normal cervix and CACX cell lines. However, the deletion status of ROBO3 and ROBO4 in tumor is not known.…”

MicroRNA-218 inhibits cell invasion and migration of pancreatic cancer via regulating ROBO1

“…20 Although it was recognized as pivotal regulator in the development of central nervous system, 21 slit/ROBO1 signal was also reported to play a role in modulating chemotaxis of T cells and tumor angiogenesis. 22,23 More evidence showed that the secreted slit2 protein mediated chemorepulsive signal on ROBO1 expressing cells, and a chemorepulsive mechanism induced by the interaction between slit2 and ROBO1 might drive glioma and breast cancer cells migration.…”