TY - JOUR
T1 - Clinical Significance of GAB2, a Scaffolding/Docking Protein Acting Downstream of EGFR in Human Colorectal Cancer
AU - Matsumura, Tae
AU - Sugimachi, Keishi
AU - Takahashi, Yusuke
AU - Uchi, Ryutaro
AU - Sawada, Genta
AU - Ueda, Masami
AU - Hirata, Hidenari
AU - Sakimura, Shotaro
AU - Ueo, Hiroki
AU - Takano, Yuki
AU - Kurashige, Junji
AU - Shinden, Yoshiaki
AU - Eguchi, Hidetoshi
AU - Sudo, Tomoya
AU - Yamamoto, Hirofumi
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Mimori, Koshi
N1 - Funding Information:
ACKNOWLEDGMENT We thank T. Shimooka, K. Oda, M. Ka-sagi, and S. Kono for their technical assistance. This work was supported in part by the following grants and foundations: CREST, Japan Science and Technology Agency (JST); Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research, Grant Numbers 25430111, 25461953, 25861199, 25861200; Japan Science and Technology Agency (JSTA) A-step, Grant AS242Z03987P; and the Founding Program for Next Generation World-leading Researchers (LS094).
Publisher Copyright:
© 2014, Society of Surgical Oncology.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1245/s10434-014-3889-x
DO - 10.1245/s10434-014-3889-x
M3 - Article
C2 - 25029990
AN - SCOPUS:84939879615
SN - 1068-9265
VL - 21
SP - 743
EP - 749
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 4
ER -
