Department of Biochemistry and Molecular Biology, UF-Shands Cancer Center, College of Medicine, University of Florida, 1600 SW Archer Road, P.O. Box 1000245, Gainesville, FL 32610, USA.
Breast Cancer Res Treat. 2013 Jan;137(2):329-36. doi: 10.1007/s10549-012-2351-7. Epub 2012 Dec 8.
Owing to numerous pro-survival target genes, aberrant activation of the NF-κB transcription factor is associated with a drug-resistant phenotype and aggressive breast tumor behavior. Transglutaminase 2 (TG2), a ubiquitously expressed protein cross-linking enzyme, activates NF-κB through a non-conventional mechanism that disables the IκBα inhibitor. Our group has recently documented that the TG2 gene (termed TGM2) is a direct transcriptional target of NF-κB. These developments uncover a novel self-reinforcing molecular feedback loop where TG2 activates NF-κB and, in turn, NF-κB directly upregulates the transcription of TGM2. This manuscript reviews the literature that supports the existence of the TG2/NF-κB signaling loop, the nature of the signal transduction that activates this loop, and the phenotypic consequences stemming from the aberrant activation of this novel signaling mechanism in breast cancer.
由于存在众多的促生存靶基因，NF-κB 转录因子的异常激活与耐药表型和侵袭性乳腺癌行为相关。转谷氨酰胺酶 2（TG2）是一种广泛表达的蛋白交联酶，通过一种非常规机制激活 NF-κB，该机制使 IκBα 抑制剂失活。我们的研究小组最近证明，TG2 基因（称为 TGM2）是 NF-κB 的直接转录靶标。这些发现揭示了一个新的自我强化的分子反馈回路，其中 TG2 激活 NF-κB，反过来，NF-κB 直接上调 TGM2 的转录。本文综述了支持 TG2/NF-κB 信号通路存在的文献，激活该通路的信号转导性质，以及源自乳腺癌中这种新型信号机制异常激活的表型后果。
