Invasion, metastasis, cytoskeleton, and small monomeric GTPases
Breast cancer, cancer cell migration and metastasis
University of Colorado, Anschutz Medical Campus, Research buildings
To study the molecular machinery regulating breast cancer cell migration, invasion and metastasis
Remodelling of the extracellular matrix (ECM) is a key process during tumor growth and metastasis and is mediated via formation of structures, known as invadopodia, and targeted secretion of enzymes, known as matrix metalloproteinases (MMPs). Invadopodia are actin-rich structures that degrade the ECM and have been shown to be important for tumor progression. MMP2/9 also have been shown to be enriched at the invadopodia and are known for their roles in breast tumor growth/metastasis. As a result, MMP2/9 have emerged as possible therapeutic targets. Unfortunately, clinical trials directly inhibiting MMP2/9 have proven ineffective, mostly due to adverse side effects and pre-existing high levels of secreted MMPs. It has been proposed that targeting the machinery specifically mediating MMP secretion at cancer cell invadopodia is more effective approach. However, little is known about targeted MMP2/9 secretion since most of the studies have focused on the mechanisms mediating ECM and cell adhesion and actin dynamics during metastasis. In contrast, very few studies have analysed the machinery mediating targeted MMP secretion in cancer cells in vitro and tested these mechanisms in vivo. The main goal of this project is to combine studies using basic cell and molecular biology techniques with more translational in vivo approaches to define and systematically analyse novel pathways that mediate targeted MMP transport and secretion during breast cancer metastasis.