Adhesion and Integrins
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 from breast cancer. The BCI αvβ6-specific peptide (A20FMDV2) is being developed for radio-imaging of human cancers.
- Batista et al. Haematopoietic focal adhesion kinase deficiency alters haematopoietic homeostasis to drive tumour metastasis. Nat Commun. 2014; 5:5054
- Elosegui-Artola et al. Rigidity sensing and adaptation through regulation of integrin types. Nature Materials. 2014; 13(6):631-7
- Moore et al. Therapeutic targeting of integrin αvβ6 in breast cancer. J Natl Cancer Inst. 2014; 106(8)
- Ramsay et al. Chronic lymphocytic leukemia cells induce defective LFA-1-directed T-cell motility by altering Rho GTPase signaling that is reversible with lenalidomide. Blood 2013; 121, (14) 2704-2714.
- Allen et al. Clinical and functional significance of α9β1 integrin expression in breast cancer: a novel cell-surface marker of the basal phenotype that promotes tumour cell invasion. J Pathol. 2011; 223(5):646-58
- Tavora et al. Endothelial FAK is required for tumour angiogenesis. EMBO Mol Med. 2010; 2, (12) 516-528
Who does the research
- Breast Cancer Campaign
- Cancer Research UK
- European Haematology Association
- Pancreatic Cancer Research Fund