November 1, 2012
Metastasis is the leading cause of death in cancer patients. Current models suggest that metastasis is a multistep process in which malignant cells escape from a primary tumor, migrate and survive in the circulatory system, and colonize distant organs. The genetic and molecular mechanisms that govern metastasis remain poorly understood. Our lab uses zebrafish neural crest cells as a model of metastatic cancer cells. Neural crest is an embryonic cell population that migrates extensively during development and forms diverse adult structures, including pigment cells, the peripheral nervous system, and components of the craniofacial skeleton. The neural crest is a good model of metastasis because both cell populations migrate to, invade, and colonize distant sites in the body.
Our research focuses on the genetic mechanisms that regulate cell migration during development and disease. Migrating cells display many actin-based cellular protrusions, including filopodia. Filopodia are thought to serve as sensory structures (or “antennae”) in migrating cells. A critical regulator of filopodia formation is the actin-bundling protein Fascin, which is highly upregulated in many human cancers and is associated with clinically aggressive tumors, metastasis, and poor outcome. We have taken a loss of function approach to study the role of Fascin in neural crest cell migration and cancer metastasis. In the zebrafish embryo, Fascin knockdown results in abnormal filopodia formation and defective neural crest migration. We are also utilizing a zebrafish tumor model developed in our lab to study the requirement for Fascin in tumor invasion and metastasis. These highly invasive tumors express high levels of Fascin and thus serve as an excellent model to interrogate the precise stage that Fascin is required in the metastatic progression.