Grant: Project Grant

Breast cancer is the most frequently diagnosed cancer worldwide and it is responsible for more female deaths than any other cancer. It is a heterogeneous disease, so tumours can have different molecular features and clinical behaviours. Highly metastatic tumours, such as those of the HER2-enriched and triple-negative/basal subtypes, are associated with the worst prognoses, thus there is intense interest in identifying new molecular targets to prevent the invasion and spread of cancer cells. We are studying the Nck1/2 family of adaptor proteins, which function as relays within the cell to transmit signals for cell movement and invasion. We have found that Nck1/2 are upregulated in HER2+ and triple-negative human tumours, and our preliminary data shows that loss of these proteins blocks metastasis in a mouse model of HER2-induced breast cancer. In parallel, we have determined that Nck1/2 regulates cell invasion during mammary gland development, and we hypothesize that these functions for Nck1/2 are subverted in cancer. In this project, we will use genetically modified mice and cultured cells to investigate molecular mechanisms of mammary epithelial cell invasion and breast cancer metastasis. Our overall goal is to determine whether Nck1/2 could serve as a prognostic indicator and/or therapeutic target in metastatic disease.