[PDF][PDF] Persistently activated Stat3 maintains constitutive NF-κB activity in tumors

H Lee, A Herrmann, JH Deng, M Kujawski, G Niu, Z Li… - Cancer cell, 2009 - cell.com
H Lee, A Herrmann, JH Deng, M Kujawski, G Niu, Z Li, S Forman, R Jove, DM Pardoll, H Yu
Cancer cell, 2009cell.com
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 …
Summary
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.
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