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Cancer Cell. 2009 Apr 7;15(4):283-93. doi: 10.1016/j.ccr.2009.02.015.

Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors.

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1
Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.

Abstract

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.

PMID:
19345327
PMCID:
PMC2777654
DOI:
10.1016/j.ccr.2009.02.015
[Indexed for MEDLINE]
Free PMC Article

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