Project No. 2324

STANDARD PROJECT

Primary Supervisor

Prof Ben Goult – University of Kent

Co-Supervisor(s)

Dr Tim Fenton – University of Southampton

Summary

Cancer metastasis is a major health problem and involves the migration and spread of cancer cells from the solid tumour to other parts of the body.

The protein Talin is the core mechanosensitive adapter protein at the heart of the cell migration machinery. Talin was previously considered to be expressed as a single isoform. However, we have just discovered a cancer-enriched, non-annotated 51 nucleotide exon in talin.

Excitingly, since discovering this new form of talin, we have found that inclusion/exclusion of the novel talin exon correlates with different responses to breast cancer treatments – inclusion of the exon results in increased sensitivity to EGFR inhibitors, whereas cell lines that lack this exon are resistant to drugs targeting PI3K signaling. Thus, our data indicates that this novel exon correlates with responses to a variety of drugs, suggesting that the exon status may support prediction of therapeutic success.
The aim of this project is to understand a) how this exon effects talin structure and function b) why does altered talin lead to altered drug responses, c) what are the signals that control this altered splicing event, d) can we develop an assay to read the status of this exon for use in cancer diagnostics and biopsies?

The project will use a multi-disciplinary approach combining biochemistry (Kent) and cancer biology (Soton) to understand how this exon is controlling cells to the extent that it can identify which drugs a cancer will respond to.
The successful completion of this project will define novel cancer cell biology and a new mode of cellular regulation and provide a novel strategy for stratifying cancer subtypes which may help with personalized medicine for targeted treatment of breast cancer.