The expression of small, non-coding RNA or microRNAs (miR), is frequently 
deregulated in human cancer, but how these pathways affect disease progression 
is still largely elusive. Here, we report on a miR, miR-296, which is 
progressively lost during tumor progression and correlates with metastatic 
disease in colorectal, breast, lung, gastric, parathyroid, liver and bile ducts 
cancers. Functionally, miR-296 controls a global cell motility gene signature in 
epithelial cells by transcriptionally repressing the cell polarity-cell 
plasticity module, Scribble (Scrib). In turn, loss of miR-296 causes aberrantly 
increased and mislocalized Scrib in human tumors, resulting in exaggerated 
random cell migration and tumor cell invasiveness. Re-expression of miR-296 in 
MDA-MB231 cells inhibits tumor growth in vivo. Finally, miR-296 or Scrib levels 
predict tumor relapse in hepatocellular carcinoma patients. These data identify 
miR-296 as a global repressor of tumorigenicity and uncover a previously 
unexplored exploitation of Scrib in tumor progression in humans.