Metastasis is one of the typical features of malignancy that significantly 
increases cancer-related mortality. Recent studies have shown that 
epithelial-mesenchymal transition (EMT) is closely related to the invasion and 
migration of cancer cells. Grainyhead-like 2 (Grhl2), a transcription factor, 
has been reported to be associated with several tumor processes including EMT. 
In the previous study, we have reported that Grhl2 functioned as a tumor 
suppressor in proliferation and apoptosis of gastric cancer. Here we aim to 
explore the effects of Grhl2 on invasion and migration of gastric cancer and 
further clarify its possible underlying mechanisms. As a result, in both SGC7901 
and MKN45 cells, Grhl2 overexpression significantly inhibited the ability of 
invasion and migration. In addition, preliminary experiments showed that Grhl2 
reduces the protein expression of matrix metalloproteinase-2, -7 and -9 (MMP-2, 
MMP-7 and MMP-9). Most importantly, Grhl2 antagonizes transforming growth 
factor-β (TGFβ)-induced EMT, and inhibition of TGFβ signaling pathways can 
restore Grhl2 expression. Finally, the results of subcutaneous xenograft model 
indicated that Grhl2 suppresses the growth of gastric cancer and reverses EMT 
process in vivo. Meanwhile, the metastatic tumor model further confirmed the 
inhibition of Grhl2 on metastasis of gastric cancer. Taken together, our 
findings proved that Grhl2, functioned as a tumor suppressor, reduces the 
invasion and migration through inhibition of TGFβ-induced EMT in gastric cancer.