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2018 ; 6
(2
): ä Nephropedia Template TP
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Subunit-Specific Role of NF-?B in Cancer
#MMPMID29673141
Kaltschmidt B
; Greiner JFW
; Kadhim HM
; Kaltschmidt C
Biomedicines
2018[Apr]; 6
(2
): ä PMID29673141
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The transcription factor NF-κB is a key player in inflammation, cancer
development, and progression. NF-κB stimulates cell proliferation, prevents
apoptosis, and could promote tumor angiogenesis as well as metastasis. Extending
the commonly accepted role of NF-κB in cancer formation and progression,
different NF-κB subunits have been shown to be active and of particular
importance in distinct types of cancer. Here, we summarize overexpression data of
the NF-κB subunits RELA, RELB, and c-REL (referring to the v-REL, which is
the oncogene of Reticuloendotheliosis virus strain T) as well as of their
upstream kinase inhibitor, namely inhibitor of κB kinases (IKK), in
different human cancers, assessed by database mining. These data argue against a
universal mechanism of cancer-mediated activation of NF-κB, and suggest a
much more elaborated mode of NF-κB regulation, indicating a tumor
type-specific upregulation of the NF-κB subunits. We further discuss recent
findings showing the diverse roles of NF-κB signaling in cancer development
and metastasis in a subunit-specific manner, emphasizing their specific
transcriptional activity and the role of autoregulation. While non-canonical
NF-κB RELB signaling is described to be mostly present in hematological
cancers, solid cancers reveal constitutive canonical NF-κB RELA or c-REL
activity. Providing a linkage to cancer therapy, we discuss the recently
described pivotal role of NF-κB c-REL in regulating cancer-targeting immune
responses. In addition, current strategies and ongoing clinical trials are
summarized, which utilize genome editing or drugs to inhibit the NF-κB
subunits for cancer treatment.