Copyright ©2012 Baishideng Publishing Group Co.
World J Gastroenterol. Aug 21, 2012; 18(31): 4071-4081
Published online Aug 21, 2012. doi: 10.3748/wjg.v18.i31.4071
Figure 1
Figure 1 Role of inflammation- and stress-related signaling pathways in hepatocarcinogenesis. Chronic liver damage induces a persistent cycle of necro-inflammation and hepatocyte regeneration, resulting in genetic mutations in hepatocytes and expansion of initiated cells, eventually leading to hepatocellular carcinoma (HCC) development. As shown in the figure, nuclear factor-κB, signal transducer and activator of transcription 3, and stress-activated mitogen-activated protein kinase pathways play critical roles in these processes. Furthermore, other factors, such as obesity and impaired expression of microRNA, can modify these inflammatory processes and accelerate HCC development. ROS: Reactive oxygen species; TLR: Toll-like receptor; NF-κB: Nuclear factor-κB; TNF: Tumor necrosis factor; IL: Interleukin; JNK: c-Jun NH2 terminal kinase; STAT: Signal transducer and activator of transcription.
Figure 2
Figure 2 Implications and regulatory system of interleukin-6/gp130/janus activated kinase/signal transducer and activator of transcription 3 signaling in hepatocarcinogenesis. Interleukin (IL)-6 secreted by Kupffer cells activates signal transducer and activator of transcription (STAT) 3, which promotes the proliferation and survival of initiated hepatocytes. STAT3 activation is suppressed by I κB kinase β through the prevention of reactive oxygen species. However, once STAT3 is activated, STAT3 activation becomes sustained through a microRNA feedback inflammatory loop. JAK: Janus activated kinase; SOCS3: Suppressor of cytokine signaling 3; IKK: I κB kinase; HNF: Hepatocyte nuclear factor; ROS: Reactive oxygen species.