The Unsolved Puzzle of c-Rel in B Cell Lymphoma

Kober-Hasslacher, Maike; Schmidt-Supprian, Marc

doi:10.3390/cancers11070941

Cited by 13 publications

(9 citation statements)

References 162 publications

(251 reference statements)

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“…paracrine production of inflammatory cytokines. 1,18,39 Some members of the NF-kB family are directly oncogenic, including c-Rel, which consistently transforms cells in culture and is amplified in lymphomas 43 and v-Rel protein, which leads to rapidly fatal lymphoma/leukemia in birds. 29 Other known oncogenes that signal through NF-kB and lead to its overactivation include Ras, myc, Pim-2 (a transcriptionally regulated oncogenic kinase), and various viral proteins, including Kaposi's sarcoma-associated herpesvirus, hepatitis B virus protein HBx, Epstein-Barr Virus latent membrane protein, and human T-lymphocytic leukemia virus 1.…”

Section: Nf-kb Dysregulation and Cancer Developmentmentioning

confidence: 99%

Review: NF-kB activation in canine cancer

Schlein

Thamm

2022

Vet Pathol

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Spontaneous tumors in dogs share several environmental, epidemiologic, biologic, clinical and molecular features with a wide variety of human cancers, making this companion animal an attractive model. Nuclear factor kappa B (NF-kB) transcription factor overactivation is common in several human cancers, and there is evidence that similar signaling aberrations also occur in canine cancers including lymphoma, leukemia, hemangiosarcoma, mammary cancer, melanoma, glioma, and prostate cancer. This review provides an overview of NF-kB signaling biology, both in health and in cancer development. It also summarizes available evidence of aberrant NF-kB signaling in canine cancer, and reviews antineoplastic compounds that have been shown to inhibit NF-kB activity used in various types of canine cancers. Available data suggest that dogs may be an excellent model for human cancers that have overactivation of NF-kB.

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Section: Nf-kb Dysregulation and Cancer Developmentmentioning

confidence: 99%

Review: NF-kB activation in canine cancer

Schlein

Thamm

2022

Vet Pathol

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“…All these genes, including REL, were located in the 2p15-16.1 chromosome region when amplified and in the 22q11.22 chromosome region when deleted (Supplementary Table S9). Amplification of 2p15-16.1 chromosome region could be expected (24) and is associated with transformation from follicular lymphoma to DLBCL (25). Deletion of the 22q region was reported once and could be associated in DLBCLs with a more advanced clinical stage (26).…”

Section: The C-rel Signature Is Associated With Decreased Genomic Commentioning

confidence: 97%

c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study

et al. 2021

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Relationships between c-Rel and GCB-DLBCLs remain unclear. We found that strong c-Rel DNA-binding activity was mostly found in GCBs on two independent series of 48 DLBCLs and 66 DLBCLs, the latter issued from the GHEDI series. c-Rel DNA-binding activity was associated with increased REL mRNA expression. Extending the study to the whole GHEDI and Lenz DLBCL published series of 202 and 233 cases, it was found that the c-Rel gene expression profile (GEP) overlapped partially (12%) but only with the GCB GEP and not with the GEP of ABC-DLBCLs. Cases with both overexpression of REL mRNA and c-Rel GEP were defined as those having a c-Rel signature. These cases were GCBs in 88 and 83% of the GHEDI or Lenz’s DLBCL series respectively. The c-Rel signature was also associated with various recurrent GCB-DLBCL genetic events, including REL gains, BCL2 translocation, MEF2B, EZH2, CREBBP, and TNFRSF14 mutations and with the EZB GCB genetic subtype. By CGH array, the c-Rel signature was specifically correlated with 2p15-16.1 amplification that includes XPO1, BCL11A, and USP34 and with the 22q11.22 deletion that covers IGLL5 and PRAME. The total number of gene copy number aberrations, so-called genomic imbalance complexity, was decreased in cases with the c-Rel signature. These cases exhibited a better overall survival. Functionally, overexpression of c-Rel induced its constitutive nuclear localization and protected cells against apoptosis while its repression tended to increase cell death. These results show that, clinically and biologically, c-Rel is the pivotal NF-κB subunit in the GCB-DLBCL subgroup. Functionally, c-Rel overexpression could directly promote DLBCL tumorigenesis without need for further activation signals.

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“…As outlined above, inflammation and tumorigenesis are often associated with the activation of the NF-κB signaling pathway. The number of NF-κB target genes is enormous and still growing, and the components and signaling molecules of these pathways were superbly reviewed in the NF-κB special issue of this journal [14,18,19,20]; that is why we will focus on some of the specific aspects in PDAC. NF-κB activity induces the secretion of cytokines and growth factors, contributing to tumor progression on one hand through the recruitment of immune cells, and on the other hand by cell intrinsic effects directly mediating apoptosis inhibition [21].…”

Section: Nf-κb Signaling In Pdacmentioning

confidence: 99%

NF-κB Dependent Chemokine Signaling in Pancreatic Cancer

Geismann¹,

Schäfer²,

Gundlach³

et al. 2019

Cancers

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Pancreatic cancer is one of the carcinomas with the worst prognoses, as shown by its five-year survival rate of 9%. Although there have been new therapeutic innovations, the effectiveness of these therapies is still limited, resulting in pancreatic ductal adenocarcinoma (PDAC) becoming the second leading cause of cancer-related death in 2020 in the US. In addition to tumor cell intrinsic resistance mechanisms, this disease exhibits a complex stroma consisting of fibroblasts, immune cells, neuronal and vascular cells, along with extracellular matrix, all conferring therapeutic resistance by several mechanisms. The NF-κB pathway is involved in both the tumor cell-intrinsic and microenvironment-mediated therapeutic resistance by regulating the transcription of a plethora of target genes. These genes are involved in nearly all scenarios described as the hallmarks of cancer. In addition to classical regulators of apoptosis, NF-κB regulates the expression of chemokines and their receptors, both in the tumor cells and in cells of the microenvironment. These chemokines mediate autocrine and paracrine loops among tumor cells but also cross-signaling between tumor cells and the stroma. In this review, we will focus on NF-κB-mediated chemokine signaling, with an emphasis on therapy resistance in pancreatic cancer.

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The Unsolved Puzzle of c-Rel in B Cell Lymphoma

Cited by 13 publications

References 162 publications

Review: NF-kB activation in canine cancer

Review: NF-kB activation in canine cancer

c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study

NF-κB Dependent Chemokine Signaling in Pancreatic Cancer

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