title: Proteomic identification of the heterogeneous nuclear ribonucleoprotein K as irradiation responsive protein related to migration.
abstract: Irradiation resistance is a major obstacle of head and neck squamous cell carcinoma (HNSCC) therapy, limiting treatment success and patient survival. The aim of our experiments was to identify irradiation-regulated proteins as potential drug targets. Two established HNSCC cell lines (HNSCCUM-01T and HNSCCUM-02T) were treated with a single 8Gy (Gray) fraction of irradiation. Changes in cellular protein expression were studied after 24h by means of 2D-electrophoresis and MALDI-TOF-mass spectrometry. Ninety-four differentially expressed proteins were identified. The expression levels of four proteins were regulated similarly in both cell lines after irradiation treatment, i.e., GRP78, PRDX, ACTC, and the heterogeneous nuclear ribonucleoprotein K (hnRNPK), suggesting a relevant role during irradiation response. hnRNPK as a p53 interacting protein was verified by Western blotting and immunocytochemical staining as well as functionally analyzed. Knock-down by the use of siRNA resulted in only slightly reduced viability, however, migratory activity was strongly reduced. Combined application of siRNA against hnRNPK and irradiation reduced migration almost completely. We conclude that hnRNPK is potentially implicated in the radiogenic response of HNSCC. The inhibition of hnRNPK might reduce the metastasizing potential of HNSCC especially in combination with irradiation and suggest that this molecule should be further evaluated in this context.
  
  
  CONCLUSIONS
  We showed completely impaired migration of irradiated hnRNPK-knock-out HNSCC cells, suggesting this molecule as a potential drug target in combined treatment schedules.
authors.affiliation: Molecular Tumor Biology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Strozynski
authors.affiliation: Molecular Tumor Biology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Heim
authors.affiliation: Molecular Tumor Biology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Sacarin
authors.initials: S
authors.lastname: Bunbanjerdsuk
authors.affiliation: Molecular Tumor Biology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Wiesmann
authors.affiliation: Molecular Tumor Biology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Lea
authors.initials: L
authors.lastname: Zografidou
authors.affiliation: Molecular Tumor Biology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Simone Katharina
authors.initials: SK
authors.lastname: Becker
authors.affiliation: Molecular Tumor Biology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Meierl
authors.affiliation: Molecular Tumor Biology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Haralampos
authors.initials: H
authors.lastname: Gouveris
authors.affiliation: Molecular Psychopharmacology, Department of Psychiatry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Lüddens
authors.affiliation: Experimental Ophthalmology, Dept. of Ophthalmology, University of Mainz, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Grus
authors.affiliation: Molecular Tumor Biology, Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. Electronic address: juergen.brieger@unimedizin-mainz.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brieger
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D006801:Humans; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D040901:Proteomics; D012261:Ribonucleoproteins / Q000096:biosynthesis*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D009363:Neoplasm Proteins; D012261:Ribonucleoproteins; C072074:HNRNPK protein, human
keywords: HNSCC; Irradiation; Migration; hnRNPK