Role of JAK/Stat signaling during zebrafish neural crest delamination and migration

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 DESCRIPTION (provided by applicant) Metastasis is the leading cause of death in cancer patients, yet we fail to understand the fundamental mechanisms of this process to develop effective therapies to interfere with its progression. One mechanism that tumors use frequently is their ability to hijack embryonic programs to increase their plasticity to leave the primary tumor, migrate long distances and grow at distant sites. To achieve this, cancerous cells induce embryonic genes to turn on signaling pathways that play roles in cell adhesion, migration, and proliferation. One such pathway that plays essential roles both during embryogenesis and in the adult is the evolutionarily conserved JAK/STAT pathway. JAK/STAT signaling is involved in various biological processes including proliferation, immunity, apoptosis and cell migration and is also often implicated cancer metastasis. However, its precise role during cell migration and metastasis is still not well understood. In order to understand the precise role of this pathway during cell migration, I will use zebrafish neural crest migration as an in vivo model. Given the remarkable similarities between these embryonic cells and invasive tumor cells, this also holds the promise of providing a powerful in vivo model to study cancer metastasis. First, I will identif the relevant JAK/STAT pathway components during neural crest migration. Then I will isolate downstream JAK/STAT target genes and other interactors during neural crest migration. Lastly, I will test the effects of the JAK/STAT pathway specifically on melanoma. The results of this proposal will significantly enhance our understanding of the role of this pathway during cell migration both during normal development and cancer metastasis. In addition, the findings from this study will determine the effects of the JAK/STAT signaling specifically on melanoma development.