Grant: Travel Awards - Institute Community Support

Triple negative breast cancer accounts for up to 20% of all breast cancer cases. Lack of therapeutic targets makes treatment of this subtype of breast cancer challenging and results in poor outcome. In order to identify novel targets for therapy, it is necessary to understand the mechanisms involved in growth and development of this subtype of breast cancer. To address this we have developed a mouse model that recapitulates many features of human triple negative breast cancer. This provides a tool to study the events responsible for initiation and development of the disease. Notably, the mammary tumors that develop in this mouse model show loss of a genomic region corresponding to a region also absent in up to 70% of human triple negative breast cancers. The frequency of this alteration in human breast cancers supports that genes located within this region likely act in some way to suppress breast cancer formation or progression. We have identified one of these genes, called Kibra, which is involved in maintaining the normal morphology and suppresses proliferation of breast epithelial cells. Loss of Kibra, in cells derived from our mouse model as well as from human triple negative breast tumors exhibit a change in morphology associated with enhanced invasion. Importantly, loss of Kibra in breast tumors promotes an enhanced metastatic spread of these cancer cells. Based on our preliminary data, we propose that Kibra is a candidate suppressor of breast cancer and that its absence contributes to enhanced metastatic spread and poor outcome of triple negative breast cancer. Kibra could therefore become a marker for the prediction of clinical outcome or a target for the development of novel therapies for the triple negative subtype of breast cancer.