Fig 2: mRNA expression levels of MST, TGF-ß1, Smad3, Yap and CTGF among groups over time. a. MST expression levels; b. TGF-ß1 expression levels; c. Smad3 expression levels; d. Yap expression levels; e. CTGF expression levels; Exp vs BC: aa (P < 0.01), a (P < 0.05); Exp vs SY Int: bb (P < 0.01), b (P < 0.05); Exp vs SB Int: **(P < 0.01), *(P < 0.05).Abbreviations: BC, blank control; SY Con, safflower yellow pigment control; SB Con, SB431542 control; Exp, exposure; SY Int, safflower yellow pigment intervention; SB Int, SB431542 intervention; MST, mammalian STE20-like; TGF-ß1, transforming growth factor-ß1; CTGF, connective tissue growth factor.

Fig 3: Immunoblotting analysis of MST, TGF-ß1, Smad3, Yap and CTGF among groups over time. Actin was used as an internal reference. a. Protein expression levels of MST, TGF-ß1, Smad3, Yap, CTGF and actin. b. Quantification of MST protein expression in lung tissue. c. Quantification of Smad3 protein expression in lung tissue. d. Quantification of TGF-ß1 protein expression in lung tissue. e. Quantification of Yap protein expression in lung tissue. f. Quantification of CTGF protein expression in lung tissue. Exp vs BC: aa (P < 0.01), a (P < 0.05); Exp vs SY Int: bb (P < 0.01), b (P < 0.05); Exp vs SB Int: **(P < 0.01), *(P < 0.05).Abbreviations: BC, blank control; SY Con, safflower yellow pigment control; SB Con, SB431542 control; Exp, exposure; SY Int, safflower yellow pigment intervention; SB Int, SB431542 intervention; MST, mammalian STE20-like; TGF-ß1, transforming growth factor-ß1; CTGF, connective tissue growth factor.

Fig 4: Colon cancer has a higher mevalonate pathway activity than paracarcinoma tissue.a Cancer tissue has higher RNA expression of multiple enzymes of the mevalonate pathway than paracarcinoma tissue. RNA expression of the cancer tissue and the paracarcinoma tissue from the same patient are compared. (n = 10). b Western blot assays of the cancer tissue (C) and the paracarcinoma tissue (P) from the same patient. It shows cancer tissue has higher protein level of HMGCS1, HMGCR, ß-catenin, TAZ, CTGF, and CYR61 than paracarcinoma tissue. (n = 10). c Immunohistochemistry assays of the cancer tissue and the paracarcinoma tissue from the same patient. It shows cancer tissue has higher protein level of HMGCS1, HMGCR, ß-catenin, and YAP than paracarcinoma tissue. (n = 10). Data are expressed as means ± SEM. *P < 0.05 (Paracarcinoma versus Carcinoma)

Fig 5: The mevalonate pathway regulates YAP/TAZ mediated alternative Wnt signaling in vitro and in vivo.a, b Lovastatin treatment suppresses the expression of YAP/TAZ target genes, while exogenous MVA restores them. RKO (a) or SW480 (b) cells are treated with lovastatin (5 µM) or lovastatin plus MVA (0.5 mM) for 48 h, and RNA is isolated for the RT-PCR assay. c Lovastatin treatment decreased the expression of YAP in RKO cells. Cells are treated with lovastatin (5 µM) or lovastatin plus MVA (0.5 mM) for 48 h, then immunofluorescence is performed to detect the level of YAP. d Lovastatin treatment suppresses the activity of 8×GTIIC-Lux reporter, while MVA recovered it. 8×GTIIC-Lux reporter is transfected to RKO or SW480 cells, then the cells are treated with lovastatin (5 µM) or lovastatin plus MVA (0.5 mM) for 48 h, and then the luminescence is measured. e–g LPS treatment upregulated the RNA expression of CTGF and CYR61 (e) and the protein level of TAZ (f) in mouse liver. Eight to ten weeks male C57/BL6 mice were treated with vehicle (PBS) or LPS (1.5 mg/kg/day) for 7 days, then the liver is harvested for RNA isolation for RT-PCR or fixed for immunohistochemistry. TAZ staining area was quantified (g). Data are expressed as means ± SEM. *P < 0.05 (LOVA versus L + MVA; PBS versus LPS)