Dr Rod Luwor
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The gene CTTN codes for a protein called cortactin. Cortactin is “over-expressed” in many cancers, such as breast, oesophageal and head and neck carcinomas. It is also a key factor influencing how invasive gliomas are in patient brain tissue.
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\nIncreased levels of cortactin result in increased migration and invasiveness of tumours, two attributes that lead to poorer health outcomes in patients. Tumour invasion is facilitated by structures on the cancer cells called “invadopodia” (basically, “invasive feet”). We hypothesised that cortactin interacts with other factors like EGFRvIII and STAT3 (both important in glioma) to form invadopodia and promote glioma cell invasion.
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The results of our study confirmed that there was actually “collaboration” between cortactin (which helps the invadopodia form) and other factors like STAT3, which increased potential cellular invasiveness of tumours, in particular with the EGFRvIII variant in glioma cells.
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\nThese results help us to identify key genes and proteins that could be targeted in future therapies to limit the invasion of tumours, particularly some forms of glioma.
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Introducing research papers published in high-impact medical journals by members of the Brain Tumour group at the Melbourne Brain Centre.
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Glioblastoma Multiforme (GBM) is a highly aggressive brain tumour that almost always results in death. This high mortality rate is due its highly invasive nature and its resistance to both chemotherapy and radiation treatment. Thus, we are focussed on studying new genes and proteins that might be useful as therapeutic targets.
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In this study, we compared the levels of gene expression from GBM tissue associated with poor survival rates and GBM tissue obtained from people with better outcomes. It was found that a particular gene, coding for the insulin-like growth factor-binding protein 3 (IGFBP3), was more prevalent in GBM tissue associated with poor outcomes. In the laboratory, we decreased the expression of this IGFBP3 in GBM tumour cell lines. This reduced the GBM tumour growth and migration, as well as making the GBM tumour cells more susceptible to conventional cancer treatments like temozolomide and radiotherapy. Our findings indicate that IGFBP3 is important in many processes in GBM tumour growth and invasion and may be an effective therapeutic target.
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