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

Dylan Z. Kelley, Emily L. Flam, Theresa Guo, Ludmila V. Danilova, Fernando T. Zamuner, Craig Bohrson, Michael Considine, Eric J. Windsor, Justin A. Bishop, Chi Zhang, Wayne M. Koch, David Sidransky, William H. Westra, Christine H. Chung, Joseph A. Califano, Sarah Wheelan, Alexander V. Favorov, Liliana Florea, Elana J. Fertig, Daria A. Gaykalova

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)109-119
Number of pages11
JournalTranslational Research
Volume202
DOIs
StatePublished - Dec 2018

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Biochemistry, medical
  • Physiology (medical)

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    Kelley, D. Z., Flam, E. L., Guo, T., Danilova, L. V., Zamuner, F. T., Bohrson, C., Considine, M., Windsor, E. J., Bishop, J. A., Zhang, C., Koch, W. M., Sidransky, D., Westra, W. H., Chung, C. H., Califano, J. A., Wheelan, S., Favorov, A. V., Florea, L., Fertig, E. J., & Gaykalova, D. A. (2018). Functional characterization of alternatively spliced GSN in head and neck squamous cell carcinoma. Translational Research, 202, 109-119. https://doi.org/10.1016/j.trsl.2018.07.007