The guidance cues are semaphorins, soluble and cell surface molecules that have homology to Met, a scatter factor (SF) receptor tyrosine kinase. Met and semaphorins also share homology with the extracellular domain of semaphorin receptors, known as plexins. Because plexins and semaphorins are expressed outside the nervous system, Giordano et al. examined what function they might control in other tissues.
They found that ligand stimulation of a plexin in epithelial cells caused invasive growth, including scattering and anchorage-independent growth. Met is the only kinase known to trigger invasive growth and, as expected, without Met, this plexin-stimulated growth was blocked. Epithelial cells seem primed for crosstalk between the two receptors, as Met and plexin were in a preformed complex, mediated by their conserved domains. SF and semaphorins in combination produced a stronger response than either alone. “These two modalities of activation can cooperate for certain biological responses but not for others, and this could be a way to fine tune responses such as invasion, without interfering with growth,” says Giordano. ▪