Persistently Activated Stat3 Maintains Constitutive NF-κB Activity in Tumors

Heehyoung Lee, Andreas Herrmann, Jie Hui Deng, Maciej Kujawski, Guilian Niu, Zhiwei Li, Steve Forman, Richard Jove, Drew M. Pardoll, Hua Yu

Research output: Contribution to journalArticlepeer-review


NF-κB (RelA) is constitutively active in many cancers, where it upregulates antiapoptotic and other oncogenic genes. While proinflammatory stimulus-induced NF-κB activation involves IKK-dependent nuclear translocation, mechanisms for maintaining constitutive NF-κB activity in tumors have not been elucidated. We show here that maintenance of NF-κB activity in tumors requires Stat3, which is also frequently constitutively activated in cancer. Stat3 prolongs NF-κB nuclear retention through acetyltransferase p300-mediated RelA acetylation, thereby interfering with NF-κB nuclear export. Stat3-mediated maintenance of NF-κB 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-κB interaction is thus central to both the transformed and nontransformed elements in tumors.

Original languageEnglish (US)
Pages (from-to)283-293
Number of pages11
JournalCancer cell
Issue number4
StatePublished - Apr 7 2009



ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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