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.
Subject(s)
Cell Movement/physiology , Endothelium, Vascular/metabolism , Glycoproteins/physiology , Neoplasms/blood supply , Neoplasms/pathology , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/physiopathology , Nerve Tissue Proteins/physiology , Receptors, Immunologic/physiology , Amino Acid Sequence , Animals , Endothelium, Vascular/pathology , Endothelium, Vascular/physiopathology , Humans , Molecular Sequence Data , Neoplasms/metabolism , Neovascularization, Pathologic/pathology , Roundabout ProteinsABSTRACT
Although protein disulphide isomerase (PDI) has been known for nearly 40 years, several new PDIs have recently been described that reveal a remarkable diversity in both structure and function. This article reviews our current knowledge of the PDI family members and identifies four novel PDIs in the human genome. These include human transmembrane proteins that have C. elegans or Drosophila orthologues for which a developmental role has been proven. Their role in development, together with other functional roles for PDIs such as conferring resistance to apoptosis under hypoxia and a potential role in the oxygen-sensing apparatus are discussed.
