Fig. 5: p-EMT is a novel target to SBC.

a, b The construction of stable UM-chor1 cell line with TGFBI overexpression (OE) and knockdown (shRNA). The protein level of TGFBI consists with that of ZEB2. Overexpression of TGFBI increased the invasiveness of the UM-Chor1 through the p-EMT program, and vice versa. The results of quantification were shown on the right side. Scale bar, 200 μm. ***P-value ≤ 0.001. c IF images of representative SBC tumors stained for p-EMT markers TGFBI and the malignant cell-specific marker TBXT. Scale bar, 100 μm. d, e Four TGF-βR1 inhibitors (LY364947, Vactosertib, PF06952229, and YL-13027) repressed the p-EMT-like program, including the decrease of ZEB2 and TGFBI in both protein and mRNA levels. ***P-value ≤ 0.001. f Four TGF-βR1 inhibitors could attenuate the invasiveness of UM-Chor1, suggesting p-EMT as a drug target in vitro. The results of quantification were shown on the right side. Scale bar, 200 μm. ***P-value ≤ 0.001; **P-value ≤ 0.01, *P-value ≤ 0.05. g YL-13027 treatment resulted in a significant reduction in the growth of UM-Chor1 xenograft. The administration of YL-13027 started on day 21. h The HE and IHC showed TGFBI was significantly decreased after YL-13027 treatment in vivo. The expression score of TGFBI was calculated by Qupath and was shown on the right side. Scale bar, 200 μm. ***P-value ≤ 0.001.