title: ALY as a potential contributor to metastasis in human oral squamous cell carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kasamatsu
authors.forename: Ayumi
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yokoe
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ogawara
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiiba
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C105242:ALYREF protein, human; D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014157:Transcription Factors