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Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
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Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics

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

Dylan Z Kelley1, Emily L Flam1, Theresa Guo1

  • 1Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Translational Research : the Journal of Laboratory and Clinical Medicine
|August 18, 2018
PubMed

Insights

Alternative splicing events (ASEs) in head and neck squamous cell carcinoma reveal a tumor-specific GSN gene splice variant. This variant, ASE-GSN, correlates with increased invasion and may serve as a novel biomarker and neoantigen for treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Head and neck squamous cell carcinoma (HNSCC) exhibits dysregulated protein expression due to alternative splicing events (ASEs).
  • Tumor-specific alternative splicing in the GSN gene was identified in HNSCC samples.

Purpose of the Study:

  • To characterize ASEs in HNSCC.
  • To investigate the functional role of GSN gene splice variants in HNSCC.
  • To explore the potential of ASE-GSN as a diagnostic biomarker and therapeutic target.

Main Methods:

  • Characterization of alternative splicing events in HNSCC tumor samples.
  • In vitro studies to assess the functional impact of GSN isoforms (ASE-GSN and WT-GSN) on cell proliferation and invasion.
  • Analysis of isoform expression interplay.

Main Results:

  • High prevalence of ASEs observed in HNSCC tumors, including a tumor-specific variant of the GSN gene (ASE-GSN).
  • ASE-GSN expression inversely correlated with cell proliferation but correlated with increased cellular invasion.
  • Expression changes in one GSN isoform induced compensatory changes in the other.

Conclusions:

  • The balance and overall expression of GSN isoforms, particularly ASE-GSN, mediate proliferation and invasion in HNSCC.
  • Increased ASE-GSN expression is specific to cancer tissues, suggesting its potential as a biomarker for disease and progression.
  • ASE-GSN is proposed as a potential neoantigen for targeted HNSCC therapy.

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