title: A novel role for keratin 17 in coordinating oncogenic transformation and cellular adhesion in Ewing sarcoma.
abstract: Oncogenic transformation in Ewing sarcoma is caused by EWS/FLI, an aberrant transcription factor fusion oncogene. Glioma-associated 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.
authors.affiliation: Department of Oncological Sciences, Huntsman Cancer Institute, School of Medicine, University of Utah.
authors.forename: Savita
authors.initials: S
authors.lastname: Sankar
authors.forename: Jason M
authors.initials: JM
authors.lastname: Tanner
authors.forename: Russell
authors.initials: R
authors.lastname: Bell
authors.forename: Aashi
authors.initials: A
authors.lastname: Chaturvedi
authors.forename: R Lor
authors.initials: RL
authors.lastname: Randall
authors.forename: Mary C
authors.initials: MC
authors.lastname: Beckerle
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Lessnick
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053537:Keratin-17 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034802:RNA-Binding Protein EWS / Q000235:genetics / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: C106031:EWS-FLI fusion protein; C400551:GLI1 protein, human; D053537:Keratin-17; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D051057:Proto-Oncogene Proteins c-akt
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