TES As A Tumour Suppressor
In December 2007, Boeda, Briggs et al. showed that the third LIM domain of TES displaces Mena from its usual subcellular positions (focal adhesions or the cell leading edge). The ENA/VASP protein family (of which Mena is a member) are anchored to specific proteins within the cell by a peptide motif consisting of a Phenylalanine residue, followed by four Proline residues - known as a FPPPP motif. It is the EVH1 domains of VASP/EVL proteins that directly contact the FPPPP motif. The precise architecture of the TES:MENA binding was revealed by X-ray crystallography, and showed that the 3rd LIM domain of TES covered up the FPPPP binding site within Menas EVH1 domain. Isothermal Titration Calorimetry showed that TES has a greater affinity for Mena than its canonical FPPPP ligand, as presented in the focal adhesion protein Zyxin. Using microscopy it was shown that either over-expression of GFP-tagged TES, or just the tagged third LIM domain displaced Mena from focal adhesions and reduced mean cell velocity.
These finding were significant given that Mena is often over expressed in cancer cells, and is thought to be partly responsible for cancer cell motility, and therefore a factor is cancer Metastasis. TES is conversely, often not produced in cancer cells. It is possible that a drug designed to mimic TESs interaction with Mena could be used to prevent Metastasis and thus development of secondary tumours in cancer patients. Given this, the work was widely reported in the British press (the work was carried out by Cancer Research UK), and also in the international press.
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