NF-kappaB, an active player in human cancers.

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Xia Y, Shen S, Verma IM

NF-kappaB, an active player in human cancers.

Cancer Immunol Res. 2014 Sep;2(9):823-30. doi: 10.1158/2326-6066.CIR-14-0112.

PubMed ID
25187272 [ View in PubMed
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Abstract

NF-kappaB comprises a family of five transcription factors that form distinct protein complexes, which bind to consensus DNA sequences at promoter regions of responsive genes regulating cellular processes. The past three decades have witnessed remarkable progress in understanding the NF-kappaB signaling pathway in physiologic and pathologic conditions. The role of NF-kappaB in human cancer initiation, development, metastasis, and resistance to treatment has drawn particular attention. A significant number of human cancers have constitutive NF-kappaB activity due to the inflammatory microenvironment and various oncogenic mutations. NF-kappaB activity not only promotes tumor cells' proliferation, suppresses apoptosis, and attracts angiogenesis, but it also induces epithelial-mesenchymal transition, which facilitates distant metastasis. In certain circumstances, NF-kappaB activation may also remodel local metabolism and anergize the immune system to favor tumor growth. Suppression of NF-kappaB in myeloid cells or tumor cells usually leads to tumor regression, which makes the NF-kappaB pathway a promising therapeutic target. However, because of its vital role in various biologic activities, components of the NF-kappaB pathway need to be carefully selected and evaluated to design targeted therapies.

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