Fig. 6
TGIF2-enhanced LUAD metastasis is inhibited by dual inhibition of ERK and HDAC1. (A) Schematic procedure of the in vivo mouse xenograft experiment. Mice were intravenously injected with 2 × 106 TGIF2WT-overexpressing H1299 cells. After 12 d, mice were intraperitoneally injected with 50 mg/kg ERK inhibitor (SCH772984) and/or not intragastrically administered with 80 mg/kg HDAC1 inhibitor (MGCD0103) for 14 d. PBS was used as a control. (B) Representative lung images of different groups after inoculation for 30 d. (C) H&E staining analysis of lung metastasis in the indicated mice. Scale bars, 250 μm. (D) Percentage of metastatic area in mouse lungs. (E) IHC of E-cadherin and Vimentin expression in the indicated lung tumors (n = 4). Scale bars, 50 μm. (F) Proposed model illustrating the role of p-TGIF2 in promoting EMT and metastasis. In LUAD, activation of EGF/EGFR/ERK signaling phosphorylates TGIF2, which recruits HDAC1 and downregulates CDH1 transcription. However, dual inhibition of p-TGIF2 and HDAC1 represses the increased EMT by the p-TGIF2/HDAC1 complex. *, p < 0.05; **, p < 0.01; ***, p < 0.001. All data are representative of three repeated experiments