Sam68 regulates EMT through alternative splicing–activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene
Open Access
- 27 September 2010
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 191 (1), 87-99
- https://doi.org/10.1083/jcb.201001073
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.Keywords
This publication has 41 references indexed in Scilit:
- Sam68 Regulates a Set of Alternatively Spliced Exons during NeurogenesisMolecular and Cellular Biology, 2009
- MAP kinase signalling pathways in cancerOncogene, 2007
- The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cellsOncogene, 2007
- Regulation of CD44 Alternative Splicing by SRm160 and Its Potential Role in Tumor Cell InvasionMolecular and Cellular Biology, 2006
- The MAPK signalling pathways and colorectal cancerThe Lancet Oncology, 2005
- hnRNP H binding at the 5' splice site correlates with the pathological effect of two intronic mutations in the NF-1 and TSH genesNucleic Acids Research, 2004
- Mammary Epithelial-Mesenchymal Interaction Regulates Fibronectin Alternative Splicing via Phosphatidylinositol 3-KinasePublished by Elsevier BV ,2004
- The RNA binding protein Sam68 is acetylated in tumor cell lines, and its acetylation correlates with enhanced RNA binding activityOncogene, 2004
- Variable β-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environmentProceedings of the National Academy of Sciences of the United States of America, 2001
- Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cellsNature, 2001