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

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          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.

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          Most cited references102

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          Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells.

          Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on cellular hierarchies reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor-propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, and OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements and are sufficient to fully reprogram differentiated GBM cells to "induced" TPCs, recapitulating the epigenetic landscape and phenotype of native TPCs. We reconstruct a network model that highlights critical interactions and identifies candidate therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in GBM, provides detailed insight into underlying gene regulatory programs, and suggests attendant therapeutic strategies. PAPERCLIP: Copyright © 2014 Elsevier Inc. All rights reserved.
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            Advances in the molecular genetics of gliomas — implications for classification and therapy

            In 2016, a revised WHO classification of glioma was published, in which molecular data and traditional histological information are incorporated into integrated diagnoses. Herein, the authors highlight the developments in our understanding of the molecular genetics of gliomas that underlie this classification, and review the current landscape of molecular biomarkers used in the classification of disease subtypes. In addition, they discuss how these advances can promote the development of novel pathogenesis-based therapeutic approaches, paving the way to precision medicine.
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              Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity.

              Colon carcinoma is one of the leading causes of death from cancer and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, it was reported that a population of undifferentiated cells from a primary tumor, so-called cancer stem cells (CSC), can reconstitute the original tumor on xenotransplantation. Here, we show that spheroid cultures of these colon CSCs contain expression of CD133, CD166, CD44, CD29, CD24, Lgr5, and nuclear beta-catenin, which have all been suggested to mark the (cancer) stem cell population. More importantly, by using these spheroid cultures or freshly isolated tumor cells from multiple colon carcinomas, we now provide compelling evidence to indicate that the capacity to propagate a tumor with all differentiated progeny resides in a single CSC. Single-cell-cloned CSCs can form an adenocarcinoma on xenotransplantation but do not generate the stroma within these tumors. Moreover, they can self-renew and are capable of multilineage differentiation. Further analysis indicated that the lineage decision is dictated by phosphoinositide 3-kinase (PI3K) signaling in CSCs. These data support the hypothesis that tumor hierarchy can be traced back to a single CSC that contains multilineage differentiation capacity, and provides clues to the regulation of differentiation in colon cancers in vivo.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                11 May 2019
                May 2019
                : 11
                : 5
                : 655
                Affiliations
                [1 ]Department of Cell Biology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany; johannes.greiner@ 123456uni-bielefeld.de (J.G.); barbara.kaltschmidt@ 123456uni-bielefeld.de (B.K.)
                [2 ]Department of Gynecology and Obstetrics, and Perinatal Center, Protestant Hospital of Bethel Foundation, Burgsteig 13, 33617 Bielefeld, Germany; Constanze.Banz-Jansen@ 123456evkb.de
                [3 ]Department of General and Visceral Surgery, Protestant Hospital of Bethel Foundation, Schildescher Strasse 99, 33611 Bielefeld, Germany; tahar.benhidjeb@ 123456evkb.de (T.B.); jan.schulteamesch@ 123456evkb.de (J.S.a.E.)
                [4 ]Department for Thoracic Surgery and Pneumology, Protestant Hospital of Bethel Foundation, Burgsteig 13, 33617 Bielefeld, Germany; Morris.Beshay@ 123456evkb.de
                [5 ]Institute of Pathology, KRH Hospital Nordstadt, Haltenhoffstrasse 41, affiliated with the Protestant Hospital of Bethel Foundation, 30167 Hannover, Germany; Christine.Foerster@ 123456evkb.de (C.F.); ludwig.wilkens@ 123456krh.eu (L.W.)
                [6 ]Children’s Center, Protestant Hospital of Bethel Foundation, 33617 Bielefeld, Germany; Eckard.Hamelmann@ 123456evkb.de (E.H.); norbert.jorch@ 123456evkb.de (N.J.)
                [7 ]Scientific Director, Protestant Hospital of Bethel Foundation, Maraweg 21, 33617 Bielefeld, Germany; Fritz.Mertzlufft@ 123456evkb.de
                [8 ]Department of Urology and Center for Computer-assisted and Robotic Urology, Protestant Hospital of Bethel Foundation, Burgsteig 13, 33617 Bielefeld, Germany; Jesco.Pfitzenmaier@ 123456evkb.de
                [9 ]Department of Neurosurgery and Epilepsy Surgery, Protestant Hospital of Bethel Foundation, Burgsteig 13, 33617 Bielefeld, Germany; Matthias.Simon@ 123456evkb.de
                [10 ]Department of Orthopedics, Trauma Surgery, and Trauma Center, Protestant Hospital of Bethel Foundation, Burgsteig 13, 33617 Bielefeld, Germany; Thomas.Vordemvenne@ 123456evkb.de (T.V.); Dirk.Waehnert@ 123456evkb.de (D.W.)
                [11 ]Department of Hematology, Oncology, Internal Medicine, Bone Marrow and Stem Cell Transplantation, Palliative Medicine, and Tumor Center, Protestant Hospital of Bethel Foundation, Burgsteig 13, 33617 Bielefeld, Germany; Florian.Weissinger@ 123456evkb.de
                [12 ]Molecular Neurobiology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany
                Author notes
                [* ]Correspondence: c.kaltschmidt@ 123456uni-bielefeld.de ; Tel.: +49-521-106-5625
                [†]

                Forschungsverbund BioMedizin Bielefeld, FBMB, Maraweg 21, 33617 Bielefeld, Germany.

                Author information
                https://orcid.org/0000-0003-0409-0747
                https://orcid.org/0000-0002-0524-662X
                https://orcid.org/0000-0002-2101-5012
                Article
                cancers-11-00655
                10.3390/cancers11050655
                6563002
                31083587
                2ad0e086-c552-48fb-99f8-dfa431df492f
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 March 2019
                : 08 May 2019
                Categories
                Review

                cancer stem cells,nf-κb,glioblastoma multiforme,pediatric cancer,ovarian cancer,multiple myeloma,lung cancer,colon cancer,prostate cancer,bone cancer

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