| First Author | He G | Year | 2010 |
| Journal | Cancer Cell | Volume | 17 |
| Issue | 3 | Pages | 286-97 |
| PubMed ID | 20227042 | Mgi Jnum | J:158659 |
| Mgi Id | MGI:4439406 | Doi | 10.1016/j.ccr.2009.12.048 |
| Citation | He G, et al. (2010) Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cell 17(3):286-97 |
| abstractText | The NF-kappaB activating kinase IKKbeta suppresses early chemically induced liver tumorigenesis by inhibiting hepatocyte death and compensatory proliferation. To study IKKbeta's role in late tumor promotion and progression, we developed a transplant system that allows initiated mouse hepatocytes to form hepatocellular carcinomas (HCC) in host liver after a long latency. Deletion of IKKbeta long after initiation accelerated HCC development and enhanced proliferation of tumor initiating cells. These effects of IKKbeta/NF-kappaB were cell autonomous and correlated with increased accumulation of reactive oxygen species that led to JNK and STAT3 activation. Hepatocyte-specific STAT3 ablation prevented HCC development. The negative crosstalk between NF-kappaB and STAT3, which is also evident in human HCC, is a critical regulator of liver cancer development and progression. |
