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Transglutaminase 2 and NF-κB: an odd couple that shapes breast cancer phenotype

Abstract

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.

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Acknowledgments

The author thanks Drs. Lingbao Ai and Kapil Mehta for insightful discussions before the drafting of this manuscript. Work in our lab has been supported by grants from the NIH (R01-CA102289), the Ocala Royal Dames for Cancer Research, and the Florida Department of Health.

Conflict of interest

The author has no conflicts of interest to declare.

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Correspondence to Kevin D. Brown.

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Brown, K.D. Transglutaminase 2 and NF-κB: an odd couple that shapes breast cancer phenotype. Breast Cancer Res Treat 137, 329–336 (2013). https://doi.org/10.1007/s10549-012-2351-7

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Keywords

  • Transcription factors
  • Feedback loop
  • Cell signaling
  • Drug resistance
  • DNA damage response