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BORDER-CELL MIGRATION: THE RACE IS ON
Denise J. Montell
The conversion of stationary epithelial cells into migratory, invasive cells is important for normal embryonic development and tumour metastasis. Border-cell migration in the ovary of Drosophila melanogaster has emerged as a simple, genetically tractable model for studying this process. Three distinct signals, which are also upregulated in cancer, control border-cell migration, so identifying further genes that are involved in border-cell migration could provide new insights into tumour invasion.
During embryonic development there are numerous occasions when cells that are part of a stable epithelium lose the cellcell and cellmatrix junctions that hold them in place, acquire a less rigidly polarized morphology and break away from their neighbours. This beautiful and fascinating behaviour of normal embryonic cells is, by equal measure, ugly and destructive when acquired by tumour cells. Tumour cells that develop invasive properties can spread through surrounding tissues, find their way into the bloodstream and eventually colonize distant sites, which makes cancer far more difficult to treat. So, a thorough molecular understanding of the mechanisms that govern the conversion of stationary epithelial cells into migratory and invasive cells should not only shed light on normal embryogenesis but could also lead to better understanding, prevention and perhaps even treatment of cancer.
One strategy that has been successful in leading to a thorough molecular understanding of complex processes such as embryonic pattern formation and apoptosis is forward genetic analysis. This approach involves random mutagenesis followed by the selection or screening of mutant lines for specific defects in the process of interest. Molecular, cellular and biochemical characterization of the affected genes and proteins is then carried out. Several laboratories have used this approach to study a small group of invasive follicle cells which are known as the border cells in the Drosophila melanogaster ovary to gain insight into the genes that are required for epithelial cells to become migratory. Powerful genetic
approaches that are unique to this experimental organism have been used to identify several of the proteins that are involved in the process of border-cell migration (TABLE 1).
In this review, I describe border-cell migration and the molecular mechanisms that govern it, and focus primarily on the three recently discovered signalling pathways that control different aspects...