ALY as a potential contributor to metastasis in human oral squamous cell carcinoma

J Cancer Res Clin Oncol. 2013 Apr;139(4):585-94. doi: 10.1007/s00432-012-1361-5. Epub 2012 Dec 15.

Abstract

Purpose: ALY, an essential mRNA export factor, is dysregulated in a wide variety of human malignancies. However, little is known about the relevance of ALY to oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate ALY expression and its functional mechanisms in OSCCs.

Methods: ALY mRNA and protein expression in seven OSCC-derived cell lines (Sa3, HO-1-u-1, KON, Ca9-22, HSC-2, HSC-3, and HSC-4) and primary OSCCs were analyzed by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting, and immunohistochemistry. We evaluated cellular invasiveness, migration, and the expression levels of metastasis modulators, ribosomal RNA processing 1 homolog B (RRP1B) and CD82, in ALY knockdown cells.

Results: ALY was frequently up-regulated in OSCC-derived cell lines and primary OSCCs compared with normal counterparts at both the mRNA and protein expression levels. ALY-positive expression was correlated significantly (P < 0.05) with a higher risk of regional lymph node metastasis. Furthermore, ALY knockdown cells caused a significant (P < 0.05) decrease in cellular invasiveness and migration with up-regulation of RRP1B and CD82 compared with the control cells.

Conclusion: Our results showed that ALY is linked to regional lymph node metastasis by regulating cellular invasiveness and migration. Therefore, ALY might be a potential biomarker for early detection of lymph node metastasis in OSCCs.

Publication types

  • Comparative Study

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Case-Control Studies
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mouth Mucosa / metabolism
  • Mouth Mucosa / pathology
  • Mouth Neoplasms / diagnosis*
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Neoplasm Staging
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured

Substances

  • ALYREF protein, human
  • Biomarkers, Tumor
  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Transcription Factors