Grhl2 reduces invasion and migration through inhibition of TGFβ-induced EMT in gastric cancer

Abstract 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.