Clinical significance of GAB2, a scaffolding/docking protein acting downstream of EGFR in human colorectal cancer.

Abstract

PURPOSE:

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: Tae Matsumura, Keishi Sugimachi, Yusuke Takahashi, Ryutaro Uchi, Genta Sawada, Masami Ueda, Hidenari Hirata, Shotaro Sakimura, Hiroki Ueo, Yuki Takano, Junji Kurashige, Yoshiaki Shinden, Hidetoshi Eguchi, Tomoya Sudo, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori, Koshi Mimori
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 21 Suppl 4 Pg. S743-9 (Dec 2014) ISSN: 1534-4681 [Electronic] United States
• PMID: 25029990 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• GAB2 protein, human
• RNA, Messenger
• RNA, Small Interfering
• Phosphatidylinositol 3-Kinases
• Class I Phosphatidylinositol 3-Kinases
• PIK3CA protein, human
• ErbB Receptors

Topics

• Adaptor Proteins, Signal Transducing (analysis, genetics)
• Aged
• Blood Vessels (pathology)
• Cell Line, Tumor
• Cell Proliferation
• Class I Phosphatidylinositol 3-Kinases
• Colon (chemistry)
• Colorectal Neoplasms (chemistry, genetics, pathology)
• ErbB Receptors (analysis, genetics)
• Female
• Gene Expression
• Humans
• Liver Neoplasms (genetics, secondary)
• Lymphatic Metastasis
• Lymphatic Vessels (pathology)
• Male
• Middle Aged
• Neoplasm Invasiveness
• Phosphatidylinositol 3-Kinases (analysis, genetics)
• Prognosis
• RNA, Messenger (analysis)
• RNA, Small Interfering (genetics)
• Rectum (chemistry)
• Signal Transduction
• Survival Rate
• Transfection