Supervisor View 2

My WorkOur group is principally interested in the cellular and molecular mechanisms which drive cancers to progress to invasive or metastatic phenotypes. Our work in recent years has focused on the contribution of altered adhesion to this process, and has challenged the simple paradigm that decreased adhesion is a pre-requisite for cancer cell invasion (Leech AO et al, Ann Transl Med. 2015 Aug;3(13):184. doi: 10.3978/j.issn.2305-5839.2015.08.01). Specifically, we were the first to identify that overexpression of a particular adhesion protein, junctional adhesion molecule-A (JAM-A) in breast cancer patient tumour tissue was associated with increased risk of metastasis (McSherry et al, Int J Cancer. 2009 Sep 15;125(6):1343-51. doi: 10.1002/ijc.24498). We later showed that JAM-A overexpression drives cell migration (McSherry et al, Breast Cancer Res. 2011 Mar 23;13(2):R31. doi: 10.1186/bcr2853), a key early step in metastasis, and that JAM-A expression levels can regulate those of the important breast cancer oncogene human epidermal growth factor receptor-2/HER-2 (Brennan et al Oncogene. 2013 May 30;32(22):2799-804. doi: 10.1038/onc.2012.276). We have since developed novel insights into the potential contribution of JAM-A to clinical drug resistance to HER2-targeted therapies, and designed a novel small molecule inhibitor of JAM-A signalling which has shown promise in vitro and in pilot in vivo studies of murine cancer biology. We feel that JAM-A represents a novel pharmacological target of potential relevance to many cancers, and our ongoing studies will pursue in depth its contribution to tumourigenic signalling.