持续激活的Stat3维持肿瘤中组成型NF-κB活性。
Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors.
作者信息
Lee Heehyoung, Herrmann Andreas, Deng Jie-Hui, Kujawski Maciej, Niu Guilian, Li Zhiwei, Forman Steve, Jove Richard, Pardoll Drew M, Yu Hua
机构信息
Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
出版信息
Cancer Cell. 2009 Apr 7;15(4):283-93. doi: 10.1016/j.ccr.2009.02.015.
NF-kappaB (RelA) is constitutively active in many cancers, where it upregulates antiapoptotic and other oncogenic genes. While proinflammatory stimulus-induced NF-kappaB activation involves IKK-dependent nuclear translocation, mechanisms for maintaining constitutive NF-kappaB activity in tumors have not been elucidated. We show here that maintenance of NF-kappaB activity in tumors requires Stat3, which is also frequently constitutively activated in cancer. Stat3 prolongs NF-kappaB nuclear retention through acetyltransferase p300-mediated RelA acetylation, thereby interfering with NF-kappaB nuclear export. Stat3-mediated maintenance of NF-kappaB activity occurs in both cancer cells and tumor-associated hematopoietic cells. Both murine and human cancers display highly acetylated RelA, which is associated with Stat3 activity. This Stat3/NF-kappaB interaction is thus central to both the transformed and nontransformed elements in tumors.
核因子-κB（RelA）在许多癌症中持续激活，它会上调抗凋亡基因和其他致癌基因。虽然促炎刺激诱导的核因子-κB激活涉及依赖IKK的核转位，但肿瘤中维持核因子-κB持续活性的机制尚未阐明。我们在此表明，肿瘤中核因子-κB活性的维持需要信号转导和转录激活因子3（Stat3），其在癌症中也经常持续激活。Stat3通过乙酰转移酶p300介导的RelA乙酰化延长核因子-κB的核滞留，从而干扰核因子-κB的核输出。Stat3介导的核因子-κB活性维持在癌细胞和肿瘤相关造血细胞中均会发生。小鼠和人类癌症均显示出高度乙酰化的RelA，这与Stat3活性相关。因此，这种Stat3/核因子-κB相互作用对于肿瘤中的转化和未转化成分均至关重要。
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