The neural crest is a population of proliferative, migratory stem cells that arise at the lateral edges of the neural plate. These cells undergo an epithelial to mesenchymal transition (EMT), migrate extensively and ultimately give rise to many derivatives that are definitive of vertebrates. Importantly, many of the phenotypic and molecular characteristics of neural crest cells are shared by metastatic tumor cells. Members of the Snail family of transcriptional repressors are essential for both neural crest development and tumor progression, yet the mechanisms that control their activity are poorly understood and few of their downstream targets have been identified.
The aim of this proposal is to explore the roles that Snail family members play during neural crest formation and migration and during oncogenesis. I will investigate the functions of these molecules by assaying potential protein-protein interactions, by examining protein stability and subcellular localization, by testing their ability to bestow metastatic properties on non-invasive cancer cells, and by using cDNA macroarrays to identify crucial targets. Together, these analyses should provide essential insight into the parallels between normal developmental processes and tumor progression.
| Vernon, Ann E; Bakewell, Suzanne J; Chodosh, Lewis A (2007) Deciphering the molecular basis of breast cancer metastasis with mouse models. Rev Endocr Metab Disord 8:199-213 |
| Vernon, Ann E; LaBonne, Carole (2006) Slug stability is dynamically regulated during neural crest development by the F-box protein Ppa. Development 133:3359-70 |
