Metastasis, the spread of cells from a primary tumor to distant sites, is the main cause of death in patients with pancreatic cancer. Epithelial-mesenchymal transition (EMT), a process vital for morphogenesis during embryonic development, is attracting increasing attention from oncologists as a potential mechanism for the initial step of metastasis. Many genes implicated in EMT during embryogenesis are being discovered, one after another, to control metastasis. We are currently focusing on the characterization of the functional role and regulation of Snail/Slug transcription factors in the control of EMT. Snail is a zinc-finger transcriptional repressor that was identified in Drosophila as a suppressor of the transcription of shotgun (an E-cadherin homologue) in the control of embryogenesis. Flies and mice without Snail are lethal because of severe defects at the gastrula stage during development. Expression of Snail correlates with the tumor grade and nodal metastasis of many types of tumor and predicts a poor outcome in patients with metastatic cancer, particularly pancreatic cancer.

We are employing biochemical, molecular, and cellular approaches to study the functional regulation of Snail in breast cancer and will apply the knowledge that we gained for the prevention, diagnosis, and treatment of metastatic pancreatic cancer in a long run. The goal of our research program is to uncover altered signaling pathways that regulate metastasis in cancer and, by discovering these pathways, to identify molecules that may serve as the therapeutic targets for metastasis prevention.