Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene

Cristina Valacca, Serena Bonomi, Emanuele Buratti, Simona Pedrotti, Francisco Ernesto Baralle, Claudio Sette, Claudia Ghigna, Giuseppe Biamonti

Research output: Contribution to journalArticle

Abstract

Epithelial-to-mesenchymal transition (EMT) and its reversal (MET) are crucial cell plasticity programs that act during development and tumor metastasis. We have previously shown that the splicing factor and proto-oncogene SF2/ASF impacts EMT/MET through production of a constitutively active splice variant of the Ron proto-oncogene. Using an in vitro model, we now show that SF2/ASF is also regulated during EMT/MET by alternative splicing associated with the nonsense-mediated mRNA decay pathway (AS-NMD). Overexpression and small interfering RNA experiments implicate the splicing regulator Sam68 in AS-NMD of SF2/ASF transcripts and in the choice between EMT/MET programs. Moreover, Sam68 modulation of SF2/ASF splicing appears to be controlled by epithelial cell-derived soluble factors that act through the ERK1/2 signaling pathway to regulate Sam68 phosphorylation. Collectively, our results reveal a hierarchy of splicing factors that integrate splicing decisions into EMT/MET programs in response to extracellular stimuli.

Original languageEnglish
Pages (from-to)87-99
Number of pages13
JournalJournal of Cell Biology
Volume191
Issue number1
DOIs
Publication statusPublished - Oct 4 2010

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

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