title: Overexpression of L1CAM is associated with tumor progression and prognosis via ERK signaling in gastric cancer.
abstract: BACKGROUND
  L1 cell adhesion molecule (L1CAM), which belongs to the immunoglobulin superfamily, has recently been observed in a variety of human malignancies. However, its clinical implication in gastric cancer remains unclear. The aim of this study was to explore the role of L1CAM in gastric cancer and to analyze its correlation with tumor progression and prognosis.
  
  
  METHODS
  L1CAM expression was measured in human gastric cancer cell lines and knockdown was conducted using siRNA. Cell proliferation, invasion and migration ability was assessed in vitro. The downstream pathway of L1CAM was explored by western blot analysis. L1CAM expression was measured in 112 pairs of human gastric cancer and adjacent noncancerous tissues using real-time quantitative RT-PCR, and the correlation with clinicopathological features and prognosis was analyzed.
  
  
  RESULTS
  L1CAM downregulation by siRNA significantly decreased cell proliferation, migration, and invasion in gastric cancer cell lines. Phosphorylated ERK levels began to decline more rapidly in L1CAM knockdown cells compared with parental cells. L1CAM overexpression was significantly correlated with local tumor cell growth (P = 0.041), distant metastasis (P = 0.047), and tumor stage (P = 0.031). The overall survival in patients with high L1CAM expression was significantly shorter than that of patients with low L1CAM expression (P = 0.02).
  
  
  CONCLUSIONS
  L1CAM overexpression may be a critical prognostic factor in patients with gastric cancer, and was strongly associated with tumor proliferation, migration, and invasion through the ERK pathway. L1CAM might be an attractive therapeutic molecular target for the treatment of gastric cancer patients.
authors.affiliation: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ito
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamada
authors.forename: Chie
authors.initials: C
authors.lastname: Tanaka
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ito
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Murai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujii
authors.forename: Goro
authors.initials: G
authors.lastname: Nakayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koike
authors.forename: Shuji
authors.initials: S
authors.lastname: Nomoto
authors.forename: Michitaka
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D039842:Neural Cell Adhesion Molecule L1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D014945:Wound Healing
chemical_list: D039842:Neural Cell Adhesion Molecule L1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D048049:Extracellular Signal-Regulated MAP Kinases