Katy Teo

Project Title

The role of the ATX/LPA signalling axis in the metastatic dissemination of lobular breast cancer

Qualifications

• BSc (Med Sci) University of Glasgow 2006
• MBChB (Hons) University of Glasgow 2008
• MRCS 2011

Supervisors

Invasive lobular carcinoma (ILC) is a histological subtype accounting for 10-15% of breast cancer cases that exhibits clinico-pathologic features distinct from that of invasive ductal carcinoma (IDC). These include an unusual pattern of metastatic dissemination, poor response to standard chemotherapeutic agents and association with adverse long-term outcomes. The mechanisms driving the metastatic process in ILC remain ill defined, and delineation of these processes is necessary to highlight novel therapeutic targets that will lead to the generation of effective treatments for this patient group.

Gene expression profiling studies have shown autotaxin (ATX) to be upregulated in ILC relative to IDC, and we hypothesize that regulation of cell adhesive and motility properties by the ATX/LPA pathway is required for organ-specific metastasis in ILC. Differential expression of ATX will be confirmed in cell lines and clinical samples, and pathway analysis profiling performed to determine the proteins activated downstream of ATX in ILC. In vitro cell adhesion and migration assays will be undertaken, and validation achieved by siRNA knockdown of ATX in cell lines and the use of an ATX inhibitor. The role of ATX during invasion, intravasation and metastasis will be assessed in vivo. A quantitative proteomics approach will be used to identify additional pathways involved in ILC progression.