Epidermal growth-factor - Induced transcript isoform variation drives mammary cell migration

Wolfgang J. Köstler, Amit Zeisel, Cindy Körner, Jonathan M. Tsai, Jasmine Jacob-Hirsch, Nir Ben-Chetrit, Kirti Sharma, Hadas Cohen-Dvashi, Assif Yitzhaky, Eric Lader, Ulrich Tschulena, Gideon Rechavi, Eytan Domany, Stefan Wiemann, Yosef Yarden

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Signal-induced transcript isoform variation (TIV) includes alternative promoter usage as well as alternative splicing and alternative polyadenylation of mRNA. To assess the phenotypic relevance of signal-induced TIV, we employed exon arrays and breast epithelial cells, which migrate in response to the epidermal growth factor (EGF). We show that EGF rapidly - within one hour - induces widespread TIV in a significant fraction of the transcriptome. Importantly, TIV characterizes many genes that display no differential expression upon stimulus. In addition, similar EGF-dependent changes are shared by a panel of mammary cell lines. A functional screen, which utilized isoform-specific siRNA oligonucleotides, indicated that several isoforms play essential, non-redundant roles in EGF-induced mammary cell migration. Taken together, our findings highlight the importance of TIV in the rapid evolvement of a phenotypic response to extracellular signals. Copyright:

Original languageEnglish
Article numbere80566
JournalPLoS ONE
Volume8
Issue number12
DOIs
StatePublished - 6 Dec 2013
Externally publishedYes

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