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Review
. 2019 May 11;11(5):655.
doi: 10.3390/cancers11050655.

A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells

Christian Kaltschmidt  1 , Constanze Banz-Jansen  2 , Tahar Benhidjeb  3 , Morris Beshay  4 , Christine Förster  5 , Johannes Greiner  6 , Eckard Hamelmann  7 , Norbert Jorch  8 , Fritz Mertzlufft  9 , Jesco Pfitzenmaier  10 , Matthias Simon  11 , Jan Schulte Am Esch  12 , Thomas Vordemvenne  13 , Dirk Wähnert  14 , Florian Weissinger  15 , Ludwig Wilkens  16 , Barbara Kaltschmidt  17   18
Affiliations
Review

A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells

Christian Kaltschmidt et al. Cancers (Basel). .

Abstract

Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed.

Keywords: NF-κB; bone cancer; cancer stem cells; colon cancer; glioblastoma multiforme; lung cancer; multiple myeloma; ovarian cancer; pediatric cancer; prostate cancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
The role of NF-κB signaling pathways in cancer stem cells. Cancer stem cells (CSCs) from ovarian cancers could show CCL5-dependent activation of NF-κB p65-mediating MMP9-expression, migration, angiogenesis, and epithelial differentiation of CSCs [22] (left panel). Canonical and non-canonical NF-κB signaling in CSCs from multiple myeloma including commonly known mutations, which generate constitutive NF-κB-activity. Mutations are shown in boxes (right upper panel, modified from [23]). Development of plasma cells from pre-B cells in the bone marrow (right lower panel). Note that most authors think that NF-κB mutations are acquired during naive B cell to plasma cell differentiation, although high levels of pre-B cells in multiple myeloma patients might hint to some mutations already in present in the bone marrow.
Figure 2
Figure 2
Inflammatory signaling pathways cross-coupled to NF-κB in human cancers. Two pathways (NF-κB and STAT3) were directly activated by epigenetic mechanisms in breast CSCs. Data suggest a high correlation of pro-inflammatory signaling and tumor progression. For further details, see respective text (modified from [25]).
Figure 3
Figure 3
(A) Different organs can give rise to tumors containing cancer stem cells. (B) Prostate cancer tissue was identified by HE staining, stained with an antibody against the stem cell marker CD133 (magenta). Nuclei are stained with DAPI (blue). Prostate cancer typical single layer glands are visible in the left and right image. Note the nest-like appearance of CD 133 positive cancer stem cells within the cancerous tissue.
See this image and copyright information in PMC

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