Functional characterization of alternatively spliced GSN in head and neck squamous cell carcinoma.

Autor: Kelley DZ; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Flam EL; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Guo T; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Danilova LV; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Laboratory of Systems Biology and Computational Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia., Zamuner FT; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Bohrson C; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Considine M; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Windsor EJ; Department of Biotechnology, Maryland Holistics LLC, Ellicott City, Maryland., Bishop JA; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland., Zhang C; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Koch WM; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Sidransky D; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland., Westra WH; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland., Chung CH; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Califano JA; Head and Neck Cancer Center, Moores Cancer Center, University of California, San Diego, La Jolla, California; Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, La Jolla, California., Wheelan S; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Favorov AV; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Laboratory of Systems Biology and Computational Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia., Florea L; McKusick-Nathans Institute of Genetic Medicine, Center for Computational Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Fertig EJ; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Otolaryngology-Head and Neck Surgery (OHNS), University of California, San Francisco, California., Gaykalova DA; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: dgaykal@jhmi.edu.
Jazyk: angličtina
Zdroj: Translational research : the journal of laboratory and clinical medicine [Transl Res] 2018 Dec; Vol. 202, pp. 109-119. Date of Electronic Publication: 2018 Jul 26.
DOI: 10.1016/j.trsl.2018.07.007
Abstrakt: We have recently performed the characterization of alternative splicing events (ASEs) in head and neck squamous cell carcinoma, which allows dysregulation of protein expression common for cancer cells. Such analysis demonstrated a high ASE prevalence among tumor samples, including tumor-specific alternative splicing in the GSN gene.In vitro studies confirmed that overall expression of either ASE-GSN or wild-type GSN (WT-GSN) isoform inversely correlated with cell proliferation, whereas the high ratio of ASE-GSN to WT-GSN correlated with increased cellular invasion. Additionally, a change in expression of either isoform caused compensatory changes in expression of the other isoform. Our results suggest that the overall expression and the balance between GSN isoforms are mediating factors in proliferation, while increased overall expression of ASE-GSN is specific to cancer tissues. As a result, we propose ASE-GSN can serve not only as a biomarker of disease and disease progression, but also as a neoantigen for head and neck squamous cell carcinoma treatment, for which only a limited number of disease-specific targeted therapies currently exist.
(Copyright © 2018. Published by Elsevier Inc.)
Databáze: MEDLINE
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