Fig 2: The fold change alternations in mRNA levels. Bar diagram showing mRNA levels fold change of MCF-7 cells (I) and MCF-7 Xenograft mice (II) treated with single or combinatorial treatments relative to control. Bax, p53, caspase-3, caspase-9, Cytochrome C, and Bcl2 as apoptotic and anti-apoptotic genes (A), Beclin-1, ATG7, PI3K, and AKT as autophagic and growth proliferative signaling genes (B). Values are expressed as mean ± SE, n = 3. Data are presented as mean ± SE (error bar) of at least three independent experiments. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 compared with control (untreated -cells or -mice) groups.

Fig 3: (A-C) The protein levels of G3BP1 and P53 in L02 cells were observed by fluorescence staining. N = 3. The data are shown \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\bar x$$\end{document} ± s. * P < 0.05, compared with the normal group. # P < 0.05, compared with the model group

Fig 4: The proposed basic mechanism of the effect of edoxaban (EDX) on tumor growth and apoptosis mediated by factor Xa-PAR2. ( A ) In the absence of EDX, tissue factor (TF) expressed in inoculated Colon26 cells activates blood coagulation and inflammation in host mice, and generated factor Xa activates PAR2, whereas generated thrombin possibly activates PAR1/PAR4 on Colon26 cells and various stroma cells in the tumor microenvironment. PAR2 activation stimulates TF expression, STAT3-mediated IL-6, PAI-1, and MMP-2 production in peri-cancer cells, and RAS/PI3K/SyK/Ki67/cyclin D1 signaling pathways in tumor cells ( black upward arrows ). These affect tumor growth. In addition, thrombin-mediated PAR1 and PAR4 pathways induce p53 expression, leading to apoptosis, which may be regulated by the PAR2-dependent system. ( B ) EDX administration to mice suppresses factor Xa-mediated PAR2 activation, reducing PAR2 levels, followed by a decrease in plasma TF, IL-6, PAI-1, and MMP-2 levels and RAS/PI3K/SyK/Ki67/cyclin D1 signaling pathways ( white downward arrows ), leading to tumor growth suppression. Furthermore, suppression of PAR2 pathway activation by EDX may reduce the regulatory system against the PAR1/PAR4 pathway and may increase the p53-dependent apoptosis ( black upward arrows ).

Fig 5: G3BP1 affects ferroptosis by regulating the SLC7A11-GSH-GPX4 axis through the P53 NLS. (A) G3BP1 mRNA was detected by RT?PCR. (B-G) The levels of cell viability, LDH, ROS, MDA, GSH, and Fe2+ were detected by test kits. (H) P53 protein expression was detected by an ELISA kit. (I) SLC7A11 mRNA was detected by RT?PCR. (J-K) The protein levels of G3BP1, SLC7A11 and GPX4 were determined by western blotting. N = 3. The data are shown \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\bar x$$\end{document} ± s. * P < 0.05, compared with the normal group. # P < 0.05, compared with the model group. ? P < 0.05, compared with the P53-NLS-/- group. & P < 0.05, compared with the siRNA-G3BP1 group