Journal
ONCOGENE
Volume 31, Issue 1, Pages 27-38Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2011.209
Keywords
miR-296; Scribble; cell plasticity; tumor progression; metastases
Funding
- Doctorate School of Molecular Medicine at Universita degli Studi di Milano
- Fondazione Invernizzi
- Fondazione Berlucchi
- National Institutes of Health [HL54131, CA140043, CA78810, CA118005]
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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. Oncogene (2012) 31, 27-38; doi: 10.1038/onc.2011.209; published online 6 June 2011
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