A novel role for keratin 17 in coordinating oncogenic transformation and cewllular adhesion in ewing sarcoma

Savita Sankar, Jason M. Tanner, Russell Bell, Aashi Chaturvedi, R Randall, Mary C. Beckerle, Stephen L. Lessnick

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Oncogenic transformation in Ewing sarcoma is caused by EWS/FLI, an aberrant transcription factor fusion oncogene. Gliomaassociated oncogene homolog 1 (GLI1) is a critical target gene activated by EWS/FLI, but the mechanism by which GLI1 contributes to the transformed phenotype of Ewing sarcoma was unknown. In this work, we identify keratin 17 (KRT17) as a direct downstream target gene upregulated by GLI1. We demonstrate that KRT17 regulates cellular adhesion by activating AKT/PKB (protein kinase B) signaling. In addition, KRT17 is necessary for oncogenic transformation in Ewing sarcoma and accounts for much of the GLI1-mediated transformation function but via a mechanism independent of AKT signaling. Taken together, our data reveal previously unknown molecular functions for a cytoplasmic intermediate filament protein, KRT17, in coordinating EWS/FLI- and GLI1-mediated oncogenic transformation and cellular adhesion in Ewing sarcoma.

Original languageEnglish (US)
Pages (from-to)4448-4460
Number of pages13
JournalMolecular and Cellular Biology
Volume33
Issue number22
DOIs
StatePublished - Nov 15 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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