@article{09a11bd1adab496092d5ae8546962afd,
title = "Persistently Activated Stat3 Maintains Constitutive NF-κB Activity in Tumors",
abstract = "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.",
keywords = "CELLCYCLE",
author = "Heehyoung Lee and Andreas Herrmann and Deng, {Jie Hui} and Maciej Kujawski and Guilian Niu and Zhiwei Li and Steve Forman and Richard Jove and Pardoll, {Drew M.} and Hua Yu",
note = "Funding Information: We thank P.C. Heinrich for critical reading; S. Costa for editing; and staff members of the Analytic Microscopy Core, Pathology Research Core, DNA Synthesis Core, and Animal Research Center at City of Hope National Medical Center for their technical assistance. This study was supported by the National Institutes of Health (grants R01CA122976, R01CA115815, R01CA115674, and P50 CA107399), the Harry Lloyd Charitable Trust, the Board of Governors at City of Hope, gifts from the Topercer family, Mrs. Dorothy Needle, Mr. John Goldsmith, the Seraph Foundation, and the Janney Fund. Antibodies against Ac-RelA(K310) and Ac-RelA mutants were from W. Greene (University of California, San Francisco). FLAG-RelA plasmid DNA was kindly provided by M.W. Mayo (University of Virginia). Stat3 -deficient MEFs were from V. Poli (University of Turin). R.J., D.P., and H.Y. wish to dedicate this article in memory of Dr. Tsai-Fan Yu, a female physician-scientist active in medical science from the 1930s through the early 2000s. Her pioneering and seminal contributions to elucidating the metabolic basis and defining treatments for gout are a paragon of translational biomedical research. ",
year = "2009",
month = apr,
day = "7",
doi = "10.1016/j.ccr.2009.02.015",
language = "English (US)",
volume = "15",
pages = "283--293",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}