A novel BMX variant promotes tumor cell growth and migration in lung adenocarcinoma

Oncotarget. 2017 May 16;8(20):33405-33415. doi: 10.18632/oncotarget.16796.

Abstract

The non-receptor tyrosine kinase BMX has been reported in several solid tumors. However, the alternative splicing of BMX and its clinical relevance in lung cancer remain to be elucidated. Exon1.0 array was used to identify a novel alternative splicing of BMX, BMXΔN, which was confirmed by rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction. BMXΔN, resulting from exon skipping with excluding exon 1 to exon 8 of BMX gene, was found in 12% human lung adenocarcinoma specimens. BMXΔN is not found in paired pathologically normal lungs and positively correlated with EGFR mutation in lung adenocarcinomas. Moreover, BMXΔN increases cell proliferation, neoplastic transformation, and migratory property of human non-small cell lung cancer cells. The function of BMXΔN in lung cancer might be presumably due to enhanced ERK signaling.

Keywords: BMXΔN; cell proliferation; lung adenocarcinomas; migration; skipping variant.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Alternative Splicing*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Codon, Initiator
  • ErbB Receptors / genetics
  • Exons
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Neoplasm Staging
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism

Substances

  • Codon, Initiator
  • BMX protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Extracellular Signal-Regulated MAP Kinases