Molecular mechanisms of tumour invasion and metastasis

A key aim of our research in this area is to elucidate the molecular mechanisms regulating the expression of tum frontproteins involved in tumour progression in an attempt to identify new therapeutic targets and prognostic indicators. Much of our work concentratese on three main areas:

The role of integrins, MMPS and ADAMs in tumour invasion-Aberrant expression of proteins which interact with the extracellular matrix (ECM), such as integrins, matrix metalloproteinases (MMPs) and the disintegrin and metalloproteinase domain proteins (ADAMs), is associated with the acquisition of an invasive phenotype in Oral Squamous Cell Carcinoma. For example, the pattern of integrin expression such as αvβ6 and α9β1 changes in cancer such that they are often over-expressed in oral cancer cell lines. This therefore enhances their invasive ability, possibly through the ultimate up-regulation of matrix metalloproteinase enzymes (MMPs). We are also examining the role of ADAMs in cancer progression via possible interactions with integrins.

Genetic and regulatory alterations in cancer-We are investigating the role of epigenetic (acetylation and methylation of regulatory regions of DNA), transcriptional (the role of specific factors which influence the rate of gene transcription) and post-transcriptional (factors affecting the rate of translation of the protein of interest) regulatory mechanisms. We are particularly interested in the role of microRNA, a class of small non-coding RNA whose expression is often dramatically altered in cancer. These might be involved in regulating the expression of proteins which interact with the ECM. In parallel, we are analysing the possibility of using global microRNA expression patterns as a prognostic indicator in OSCC progression.

Metastasis-The molecular events controlling metastasis to lymph nodes are unclear. Recent work by the group has shown that lymphocyte-derived chemokines can regulate epithelial cell behaviour, including migration, and that these act through specific receptors not previously identified on epithelial cells

Research contacts:

Dr K. Hunter

Dr D. Lambert

Professor P. Speight

Dr S. Whawell

Professor P. Farthing