Regulation of CD44 alternative splicing by SRm160 and its potential role in tumor cell invasion

Chonghui Cheng, Phillip A. Sharp*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

Abstract

The multiple isoforms of the transmembrane glycoprotein CD44 are produced by alternative RNA splicing. Expression of CB44 isoforms containing variable 5 exon (v5) correlates with enhanced malignancy and invasiveness of some tumors. Here we demonstrate that SRm160, a splicing coactivator, regulates CD44 alternative splicing in a Ras-dependent manner. Overexpression of SRm160 stimulates inclusion of CD44 v5 when Ras is activated. Conversely, small interfering RNA (siRNA)-mediated silencing of SRm160 significantly reduces v5 inclusion. Immunoprecipitation shows association of SRm160 with Sam68, a protein that also stimulates v5 inclusion in a Ras-dependent manner, suggesting that these two proteins interact to regulate CD44 splicing. Importantly, siRNA-mediated depletion of CD44 v5 decreases tumor cell invasion. Reduction of SRm160 by siRNA transfection downregulates the endogenous levels of CD44 isoforms, including v5, and correlates with a decrease in tumor cell invasiveness.

Original languageEnglish (US)
Pages (from-to)362-370
Number of pages9
JournalMolecular and cellular biology
Volume26
Issue number1
DOIs
StatePublished - Jan 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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