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

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 alt...

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Bibliographic Details
Published in:Translational research : the journal of laboratory and clinical medicine 2018-12, Vol.202, p.109-119
Main Authors: Kelley, Dylan Z, Flam, Emily L, Guo, Theresa, Danilova, Ludmila V, Zamuner, Fernando T, Bohrson, Craig, Considine, Michael, Windsor, Eric J, Bishop, Justin A, Zhang, Chi, Koch, Wayne M, Sidransky, David, Westra, William H, Chung, Christine H, Califano, Joseph A, Wheelan, Sarah, Favorov, Alexander V, Florea, Liliana, Fertig, Elana J, Gaykalova, Daria A
Format: Article
Language:English
Subjects:
Alternative Splicing
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation - genetics
Cell Survival - genetics
Gelsolin - genetics
Gelsolin - metabolism
Gene Expression Regulation, Neoplastic
Humans
Models, Biological
Neoplasm Invasiveness
Neoplasm Metastasis
Squamous Cell Carcinoma of Head and Neck - genetics
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Summary: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.
ISSN:1931-5244
1878-1810
DOI:10.1016/j.trsl.2018.07.007