A mutation found in esophageal cancer alters integrin β4 mRNA splicing

Gabriel T. Kelly, Reem Faraj, Zhiyu Dai, Anne E. Cress, Ting Wang

Research output: Contribution to journalArticle

Abstract

Integrin β4 (CD104, mRNA: ITGβ4) contributes to anchoring cells to the extracellular matrix and is regulated in many cancer types where it contributes to tumor progression. One splice variant, integrin β4E, is poorly characterized. We extracted several mutations from tumor samples within ITGB4 near the splice site that controls ITGβ4E production, and computational analysis predicted six of these would alter splicing to alter ITGβ4E abundance. One of these mutations, from an esophageal squamous cell carcinoma sample, was predicted to increase splicing toward ITGβ4E. We verified this effect using a minigene, and observed that integrin β4E slows esophageal squamous cell migration while other variants enhance migration, demonstrating that integrin β4E regulation through mutations may contribute to esophageal squamous cell tumorigenesis.

Original languageEnglish (US)
Pages (from-to)726-732
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume529
Issue number3
DOIs
StatePublished - Aug 27 2020

Keywords

  • Esophageal cancer
  • Hemidesmosome
  • ITGβ4
  • Integrin
  • Mutation
  • Splicing

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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