Constitutively activated STAT3 plays a pivotal role in holding cancer stemness of HCC CSCs, which are essential for hepatoma initiation, relapse, metastasis and drug resistance.
In summary, activation of hepatic AMPK/sirtuin-1 and FGF21/β-klotho signaling pathways combined with down-regulation of STAT3/NFκB-mediated inflammatory and tumorigenic signaling pathways can explain the absence of hepatic tumors in AAV-NT mice.
TTF1, in the Form of Nanoparticles, Inhibits Angiogenesis, Cell Migration and Cell Invasion In Vitro and In Vivo in Human Hepatoma through STAT3 Regulation.
One of 3 candidate genes, Stat3, displayed dose-dependent DNA methylation changes in both 10-month mice with liver tumors as compared to those without liver tumors and 3-week sibling mice from the same exposure study, implicating Stat3 as a potential epigenetic biomarker of both early life BPA exposure and adult disease in mice.
mTORSTAT3 expression in hepatoma cells HepG2 was significantly higher than that in normal liver cells. mTOR blocking can reduce the expression of STAT3, which is also closely related to the invasion and metastasis of liver cancer cells.
These results showed a cross-talk between cyclic-AMP and JAK/STAT pathways in liver tumors and they reinforce the role of STAT3 activation in liver tumorigenesis.
Here we demonstrate that long-term (3-6 days) but not short-term (up to 1 day) IFN-gamma treatment of human hepatoma Hep3B cells attenuates IFN-alpha activation of STAT1 (signal transducers and activators of transcription factor 1), STAT2 and STAT3, but enhances IFN-gamma and interleukin 6 activation of STATs.
Interleukin-6 (IL-6) causes the rapid activation of the acute-phase response factor (APRF) in the liver of animals during acute inflammation and in cultured human hepatoma cells (HepG2) and induces the transcription of the acute-phase protein genes, e.g. alpha 2-macroglobulin (alpha 2-M).