Adhesion and Integrins

Why we focus on adhesion and integrins

Cell adhesion to the extracellular matrix and to other cells, via specialised receptors such as integrins (cell-matrix and cell-cell) and cadherins (cell-cell), is a fundamental necessity in the maintenance of normal tissue biology. In cancer, the inappropriate expression or activity of many of these receptors actively promotes cancer progression, which is why we focus on understanding this process with a view to identifying new molecular therapeutic targets.

What we do
  • We investigate dysfunctional adhesion in chronic lymphocytic leukaemia (CLL) and the potential use of immuno-modulatory drugs, which correct the dysfunction, to improve therapy of CLL.
  • We study integrins that regulate endothelial growth factors, specifically αvβ3 and αvβ5. The absence of αvβ3 and αvβ5 increases both blood vessel and tumour growth, and therapy with very low concentrations of αvβ3/αvβ5 inhibitors actually increases blood vessel growth and tumour development, suggesting caution in the use of integrin inhibitors in cancer treatment.
  • We focus on the epithelial-specific integrin αvβ6 as therapeutic target for carcinoma because it is not expressed by most normal tissues but is upregulated on many carcinomas including breast, colon, lung, pancreas and cervix making it a novel therapeutic target. We have been the first to show that αvβ6 promoted invasion, in part, by regulating matrix-metalloproteinases (MMPs). Strong expression of αvβ6 correlates with very poor prognosis in breast cancer. The BCI αvβ6-specific peptide (A20FMDV2) is being developed for radio-imaging of human cancers.
Major Funders
  • Breast Cancer Now
  • Cancer Research UK
  • DebRA
  • European Haematology Association
  • Medical Research Council
  • Pancreatic Cancer Research Fund
Key Publications