Published online Dec 28, 2014. doi: 10.3748/wjg.v20.i48.18306
Revised: July 12, 2014
Accepted: August 13, 2014
Published online: December 28, 2014
Processing time: 212 Days and 23 Hours
AIM: To explore the correlation between Twist-related protein (Twist)1, fibroblast growth factor receptor (FGFR)2 and gastric adenocarcinoma differentiation and progression.
METHODS: We evaluated Twist1 and FGFR2 in 52 gastric adenocarcinoma samples by immunohistochemistry and quantitative real time polymerase chain reaction, and analyzed the correlation between Twist1, FGFR2 and cancer differentiation. We also detected Twist1 and FGFR2 expression in gastric adenocarcinoma cell lines, and evaluated Twist1 influence on FGFR2 expression. In addition, we studied the role of FGFR2 in Twist1-promoted cancer progression, including proliferation, invasion and epithelial-mesenchymal transition (EMT).
RESULTS: Twist1 and FGFR2 were detected in almost all the gastric adenocarcinoma samples. Twist1 (P = 0.0213) and FGFR2 (P = 0.0310) mRNA levels had a significant association with gastric adenocarcinoma differentiation. Moreover, Twist1 and FGFR2 expression in poorly differentiated cells (SNU-1 and SNU-16) was notably higher than in well-differentiated cells (MKN-7 and MKN-28). In poorly differentiated gastric adenocarcinomas, FGFR2 mRNA level was significantly positively correlated with Twist1 mRNA level (P = 0.004). Twist1 was proved to promote FGFR2 by regulating Twist1 expression by knockdown and overexpression. Additionally, Twist1 could induce proliferation, invasion and EMT in gastric cancer; of these, FGFR2 was required for invasion and EMT, rather than proliferation.
CONCLUSION: Twist1 and FGFR2 are highly associated with differentiation of gastric adenocarcinoma; Twist1 can facilitate invasion and EMT in gastric adenocarcinoma via promotion of FGFR2 expression.
Core tip: The underlying mechanism of Twist1 and fibroblast growth factor receptor (FGFR)2 function in gastric cancer has not been fully elucidated. We assessed expression of Twist1 and FGFR2 in gastric adenocarcinoma tissues by immunohistochemistry and polymerase chain reaction, and demonstrated that Twist1 and FGFR2 expression was significantly associated with differentiation of gastric adenocarcinoma tissue. We found that Twist1 can function as a transcription factor to promote FGFR2 expression. Moreover, Twist1 can induce proliferation, invasion and epithelial-mesenchymal transition (EMT) of gastric cells, in which FGFR2 is required in the Twist1-induced cell invasion and EMT.