Many of the genetic mutations that occur in transformed cells have been well characterised, but less is known about how interactions between transformed cells and surrounding untransformed cells might also influence carcinogenesis. Yasuyuki Fujita and colleagues recently reported that the signalling pathways and cellular respones of RasV12-transformed epithelial cells are altered in the presence of untransformed cells. On page , this group now examines how the behaviour of cells transformed by another oncogene, Src, is influenced by their untransformed neighbours. The authors report that the interfaces between untransformed cells and cells transformed by either Ras or Src are remarkably similar, despite the fact that Ras and Src have different cellular roles. Similar to RasV12-transformed cells, the presence of untransformed neighbours causes Src-transformed cells to activate several signalling pathways and leads to their apical extrusion, which involves the activities of MAPK and myosin II. However, several differences — such as marked enhancement of focal-adhesion-kinase activation and tyrosine phosphorylation around the entire cortex of Src- but not RasV12-transformed cells — indicates that the promotion of apical extrusion by untransformed neighbours occurs by both overlapping and distinct mechanisms. How transformed cells sense their untransformed neighbours awaits elucidation in future studies.
