Regulation of invadopodium function and involvement in cancer cell invasion

Project Details

Project description: The cause of death for up to 90% of cancer patients is the metastatic spread of cancer cells from the primary tumour and the subsequent development of a secondary tumour or tumours at a distant site. Many patients normally present with symptoms relating to the localized primary disease which can be managed with a number of therapies including surgery, radiation and chemotherapy. But numerous patients return post-therapy with a developed metastatic lesion at a secondary site. The dissemination of metastatic cells involving the migration and infiltration of these invasive cells is commonly thought to require two events. This includes increased cellular motility, accompanied with the proteolytic processing of the extracellular matrix (ECM) and subsequent penetration through the surrounding tissues.

A property shared by several types of tumour cells with high invasive or metastatic potential is an ability to form structures known as invadopodia. They are dynamic actin-rich protrusions which adhere to and proteolytically degrade ECM substrates via the activities of secreted extracellular proteases. Functional (matrix-degrading) invadopodia have been observed in tumour cell lines and primary tumour cells derived from ex vivo tumour specimens from a number of cancers, primarily head and neck squamous cell carcinoma and breast cancer specimens. This suggests that there is a possible role for invadopodia in tumour cell invasion of many cancers.

Invadopodia formation and function are dependent on multiple proteins and signaling pathways. Therefore understanding how invadopodia are regulated and controlled within a tumour cell is essential and strategies aimed at disrupting invadopodia could form the basis of novel anti-invasive therapies for treating cancer patients in the future. This project will involve studies that explore the role of a number of invadopodia proteins in cancer cells, how they contribute to their invasive/metastatic phenotype and ultimately influence the cancer cell response to treatment protocols.

Potential Skills/Techniques: Cell Biology techniques including cell culture and cell transfections (overexpression and siRNA gene silencing), western blotting, zymography, immunofluorescence and immunohistochemistry, confocal microscopy, migration/invasion assays, reporter assays, ultracentrifugation, proteomics, RNA Seq, datamining