Fig. 5.

Virus-related products in the inflammatory tumor microenvironment. HBx stabilizes the transcription of Snail in the PI3K/AKT/GSK-3b pathway to mediate epithelial-to-mesenchymal transition (EMT). It also participates in the EMT process by inducing upregulation of Twist expression and activation of STAT3 transcription. In addition, HBx activates c-Src and mediates the expression of IGF2 in the SUMO pathway, or directly upregulates the expression of bHLH transcription factor E12/E47, which inhibits E-cadherin expression and induce EMT. NS3 promotes EMT by downregulating PPM1A through ubiquitination. It also enhances cancer cell invasion by activating matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2) via the ERK/p38/NF-κB signaling cascade, and interacts with p53 to inhibit p53-dependent transcription. NS4B upregulates the Snail transcription factor via the PI3K/AKT signaling pathway and induce EMT