title: Clinical significance of GAB2, a scaffolding/docking protein acting downstream of EGFR in human colorectal cancer.
abstract: OBJECTIVE
  Recent studies indicated that the scaffolding adaptor protein GAB2 (GRB2-associated binding protein 2) plays a critical role in the proliferation and migration of various cancers. This study aimed to determine the role of aberrant GAB2 expression in human colorectal cancer (CRC).
  
  
  METHODS
  Quantitative real-time reverse transcription polymerase chain reaction was used to evaluate GAB2 mRNA expression in 152 CRC tissues samples to determine the clinicopathological significance of GAB2 expression. We also performed in vitro proliferation assays using siGAB2-transfected CRC cells.
  
  
  RESULTS
  GAB2 expression in tumor colorectal tissues was significantly higher than in normal colorectal tissues (p = 0.0212). High GAB2 expression levels were associated with malignant clinicopathologic potential factors, including lymphatic invasion (p = 0.0003), venous invasion (p = 0.0170), and liver metastasis (p = 0.0144). The survival rate of patients with high GAB2 expression levels was significantly lower than that of patients with low GAB2 expression (p = 0.0074). Multivariate analysis indicated that GAB2 expression was a factor affecting lymph node metastasis. Cell proliferation was significantly suppressed by siGAB2 expression in CRC cells in vitro.
  
  
  CONCLUSIONS
  GAB2 expression was associated with lymph node metastasis and may play a role in the growth and metastasis of CRC. These results suggest that GAB2 is a potential therapeutic target in CRC.
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita, Japan, tmatsumura@beppu.kyushu-u.ac.jp.
authors.forename: Tae
authors.initials: T
authors.lastname: Matsumura
authors.forename: Keishi
authors.initials: K
authors.lastname: Sugimachi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Uchi
authors.forename: Genta
authors.initials: G
authors.lastname: Sawada
authors.forename: Masami
authors.initials: M
authors.lastname: Ueda
authors.forename: Hidenari
authors.initials: H
authors.lastname: Hirata
authors.forename: Shotaro
authors.initials: S
authors.lastname: Sakimura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ueo
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takano
authors.forename: Junji
authors.initials: J
authors.lastname: Kurashige
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shinden
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sudo
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics*; D000368:Aged; D001808:Blood Vessels / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058534:Class I Phosphatidylinositol 3-Kinases; D003106:Colon / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D034741:RNA, Small Interfering / Q000235:genetics; D012007:Rectum / Q000737:chemistry; D015398:Signal Transduction; D015996:Survival Rate; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490895:GAB2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D066246:ErbB Receptors