Activating mutations in genes of the Ras-mitogen-activated protein kinase (MAPK) 
pathway occur in approximately 30% of all human cancers; however, mutation of 
Ras alone is rarely sufficient to induce tumour development. Scribble is a 
polarity regulator recently isolated from a Drosophila screen for events that 
cooperate with Ras mutation to promote tumour progression and cell invasion. In 
mammals, Scribble regulates directed cell migration and wound healing in vivo; 
however, no role has been identified for mammalian Scribble in oncogenic 
transformation. Here we show that in human epithelial cells expressing oncogenic 
Ras or Raf, loss of Scribble promotes invasion of cells through extracellular 
matrix in an organotypic culture system. Further, we show that the mechanism by 
which this occurs is in the regulation of MAPK signalling by Scribble. The 
suppression of MAPK signalling is a highly conserved function of Scribble as it 
also prevents Raf-mediated defects in Drosophila wing development. Our data 
identify Scribble as an important mediator of MAPK signalling and provide a 
molecular basis for the observation that Scribble expression is decreased in 
many invasive human cancers.