Abstract
Transcription factor NF-κB has been extensively studied for its varied roles in cancer development since its initial characterization as a potent retroviral oncogene. It is now clear that NF-κB also plays a major role in a large variety of human cancers, including especially ones of immune cell origin. NF-κB is generally constitutively or aberrantly activated in human cancers where it is involved. These activations can occur due to mutations in the NF-κB transcription factors themselves, in upstream regulators of NF-κB, or in pathways that impact NF-κB. In addition, NF-κB can be activated by tumor-assisting processes such as inflammation, stromal effects, and genetic or epigenetic changes in chromatin. Aberrant NF-κB activity can affect many tumor-associated processes, including cell survival, cell cycle progression, inflammation, metastasis, angiogenesis, and regulatory T cell function. As such, inhibition of NF-κB has often been investigated as an anticancer strategy. Nevertheless, with a few exceptions, NF-κB inhibition has had limited success in human cancer treatment. This review covers general themes that have emerged regarding the biological roles and mechanisms by which NF-κB contributes to human cancers and new thoughts on how NF-κB may be targeted for cancer prognosis or therapy.
Highlights
Eukaryotic transcription factor NF-κB has been the subject of intense study over the past 35 years for its role in a variety of normal and pathological processes [1]
This review covers general themes that have emerged regarding the biological roles and mechanisms by which NF-κB contributes to human cancers and new thoughts on how NF-κB may be targeted for cancer prognosis or therapy
All IκB proteins consist of a series of 5–8 ANK repeats, which are protein interaction domains that interact with the Rel homology domain (RHD) sequences and block which are protein interaction domains that interact with the RHD sequences and block the the ability of NF-κB dimers to bind to DNA and translocate to the nucleus
Summary
Eukaryotic transcription factor NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) has been the subject of intense study over the past 35 years for its role in a variety of normal and pathological processes [1]. There are currently approximately 100,000 publications with information related to NF-κB. After providing some basic information on NF-κB protein structure and signaling, this review features a historical and conceptual overview of NF-κB signaling and human cancer, as well as therapeutic implications.
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