MiR-296 regulation of a cell polarity-cell plasticity module controls tumor progression

V. Vaira, A. Faversani, T. Dohi, M. Montorsi, C. Augello, S. Gatti, G. Coggi, D. C. Altieri, S. Bosari

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)27-38
Number of pages12
JournalOncogene
Volume31
Issue number1
DOIs
StatePublished - Jan 5 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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