Fig. 3

Overview on factors affecting F3 gene and TF-involved signaling pathways progressing cancer. The right and bottom parts of the figure show the positive and negative effectors affecting the expression of TF gene, with blue arrows indicating positive effectors and red arrows indicating negative effectors. Activation of the mTOR pathway, inflammatory cytokines such as TNF, activation of proto-oncogenes such as KRAS, inactivation of PTEN and P53, growth factors such as EGF, FGF and VEGF, and hypoxia are positive effectors. On the other hand microRNAs such as miR19 and miR19a are negative effectors of the expression of TF gene. The top part of the figure shows how TF works in angiogenesis, invasion, metastasis, tumor cell growth, and carcinogenesis. On the one hand, TF leads to uncontrolled growth of cancer cells by activating the JAK2-STAT5 pathway, which prevents the apoptosis of cancer cells, and on the other hand, by activating RTKs, it promotes the growth of tumor cells. TF leads to increased angiogenesis and metastasis of tumor cells by increasing VEGF and inhibiting TSP. TF activates rac1, which in turn activates PKA and regulates MAPK, leading to the growth and metastasis of cancer cells. TF activates PAR2, which in turn leads to increased angiogenesis, invasion, and metastasis of cancer cells in several ways. On the one hand, it leads to increased VEGF, bEGF, IL8, and βTGF- and, therefore angiogenesis, invasion, and metastasis of tumor cells. Moreover, it stabilizes β-catenin and causes invasion of tumor cells. PAR2 also activates MAPK and ERK1/2 pathways, and increases β-arrestin, which phosphorylates cofilin, leading to the polymerization of actin filaments at the edge of invading cells and thus increasing invasion and metastasis of tumor cells. TF activates the signaling pathways PI3K/AKT, MAPK, and FAK by binding to integrins α6β1 and β3vα