Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation.
Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation.
复制标题
DOI：
10.1016/j.ccr.2009.12.048
复制
发表时间：
2010-03-16
期刊：
影响因子：
50.3
通讯作者：
Karin M
中科院分区：
文献类型：
--
作者：
He G;Yu GY;Temkin V;Ogata H;Kuntzen C;Sakurai T;Sieghart W;Peck-Radosavljevic M;Leffert HL;Karin M
NF-κB激活激酶IKKβ通过抑制肝细胞死亡和代偿性增殖抑制早期化学诱导的肝肿瘤发生。为了研究IKKβ在晚期肿瘤促进和进展中的作用，我们开发了一种移植系统，使启动的小鼠肝细胞在宿主肝脏中经过长时间的潜伏期形成肝细胞癌（HCC）。IKKβ在起始后很长一段时间的缺失加速了HCC的发展，增强了肿瘤起始细胞的增殖。IKKβ/NF-κB的这些作用是细胞自主的，并与活性氧（ROS）积累增加相关，从而导致JNK和STAT3活化。肝细胞特异性STAT3消融术阻止HCC的发展。NF-κB和STAT3之间的负串扰在人类HCC中也很明显，是肝癌发生和进展的关键调节因子。
The NF-κB activating kinase IKKβ suppresses early chemically-induced liver tumorigenesis by inhibiting hepatocyte death and compensatory proliferation. To study IKKβ’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 IKKβ long after initiation accelerated HCC development and enhanced proliferation of tumor initiating cells. These effects of IKKβ/NF-κB were cell autonomous and correlated with increased accumulation of reactive oxygen species (ROS) that led to JNK and STAT3 activation. Hepatocyte-specific STAT3 ablation prevented HCC development. The negative crosstalk between NF-κB and STAT3, which is also evident in human HCC, is a critical regulator of liver cancer development and progression.
登录
查看更多内容
影响因子：
50.3
作者：
Bromberg J;Wang TC
通讯作者：
Wang TC
影响因子：
1.5
作者：
Calvisi, DF;Thorgeirsson, SS
通讯作者：
Thorgeirsson, SS
影响因子：
4.7
作者：
KAUFMANN, WK;RIRIE, DG;KAUFMAN, DG
通讯作者：
KAUFMAN, DG
影响因子：
8.4
作者：
Chen, Chien-Hung;Huang, Guan-Tarn;Sheu, Jin-Chuan
通讯作者：
Sheu, Jin-Chuan
影响因子：
50.3
作者：
Haybaeck J;Zeller N;Wolf MJ;Weber A;Wagner U;Kurrer MO;Bremer J;Iezzi G;Graf R;Clavien PA;Thimme R;Blum H;Nedospasov SA;Zatloukal K;Ramzan M;Ciesek S;Pietschmann T;Marche PN;Karin M;Kopf M;Browning JL;Aguzzi A;Heikenwalder M
通讯作者：
Heikenwalder M