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Role of NF-κB in Carcinogenesis and Its Therapeutic Regulation
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Role of NF-κB in Carcinogenesis and Its Therapeutic Regulation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 11837

Special Issue Editor

Dr. Gautam Sethi

grade E-Mail Website
Guest Editor
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Interests: cancer; inflammation; transcription factors; vitamin; apoptosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The master transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) plays an important role in both physiological and pathological conditions. It is an important component of the immune system, but once deregulated, it can promote tumorigenesis by altering the expression of various oncogenic genes. A number of strategies can be employed to target aberrant NF-κB activation, but efforts are still ongoing to identify specific NF-κB blockers that can be effective against various malignancies, especially in clinical studies. This issue will highlight the diverse mechanisms of NF-κB activation in tumor cells, its potential role in oncogenesis and novel approaches to targeting this transcription factor for cancer therapy.

Dr. Gautam Sethi
Guest Editor

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Keywords

  • NF-κB
  • tumorigenesis
  • metastasis
  • chemoresistance
  • pharmacological inhibition

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Published Papers (3 papers)

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Research

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16 pages, 2663 KiB  
Article
Potential Application of Leelamine as a Novel Regulator of Chemokine-Induced Epithelial-to-Mesenchymal Transition in Breast Cancer Cells
by Young Yun Jung, Jae-Young Um, Gautam Sethi and Kwang Seok Ahn
Int. J. Mol. Sci. 2022, 23(17), 9848; https://doi.org/10.3390/ijms23179848 - 30 Aug 2022
Cited by 9 | Viewed by 1801
Abstract
CXCR7 and CXCR4 are G protein-coupled receptors (GPCRs) that can be stimulated by CXCL12 in various human cancers. CXCR7/4–CXCL12 binding can initiate activation of multiple pathways including JAK/STAT and manganese superoxide dismutase (MnSOD) signaling, and initiate epithelial–mesenchymal transition (EMT) process. It is established [...] Read more.
CXCR7 and CXCR4 are G protein-coupled receptors (GPCRs) that can be stimulated by CXCL12 in various human cancers. CXCR7/4–CXCL12 binding can initiate activation of multiple pathways including JAK/STAT and manganese superoxide dismutase (MnSOD) signaling, and initiate epithelial–mesenchymal transition (EMT) process. It is established that cancer cell invasion and migration are caused because of these events. In particular, the EMT process is an important process that can determine the prognosis for cancer. Since the antitumor effect of leelamine (LEE) has been reported in various previous studies, here, we have evaluated the influence of LEE on the CXCR7/4 signaling axis and EMT processes. We first found that LEE suppressed expression of CXCR7 and CXCR4 both at the protein and mRNA levels, and showed inhibitory effects on these chemokines even after stimulation by CXCL12 ligand. In addition, LEE also reduced the level of MnSOD and inhibited the EMT process to attenuate the invasion and migration of breast cancer cells. In addition, phosphorylation of the JAK/STAT pathway, which acts down-stream of these chemokines, was also abrogated by LEE. It was also confirmed that LEE can induce an imbalance of GSH/GSSG and increases ROS, thereby resulting in antitumor activity. Thus, we establish that targeting CXCR7/4 in breast cancer cells can not only inhibit the invasion and migration of cancer cells but also can affect JAK/STAT, EMT process, and production of ROS. Overall, the findings suggest that LEE can function as a novel agent affecting the breast cancer. Full article
(This article belongs to the Special Issue Role of NF-κB in Carcinogenesis and Its Therapeutic Regulation)
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Review

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14 pages, 1611 KiB  
Review
The Role of NF-κB in Endometrial Diseases in Humans and Animals: A Review
by Łukasz Zdrojkowski, Tomasz Jasiński, Graça Ferreira-Dias, Bartosz Pawliński and Małgorzata Domino
Int. J. Mol. Sci. 2023, 24(3), 2901; https://doi.org/10.3390/ijms24032901 - 2 Feb 2023
Cited by 16 | Viewed by 2651
Abstract
The expression of genes of various proinflammatory chemokines and cytokines is controlled, among others, by the signaling pathway of the nuclear factor kappaB (NF-κB) superfamily of proteins, providing an impact on immune system functioning. The present review addresses the influence and role of [...] Read more.
The expression of genes of various proinflammatory chemokines and cytokines is controlled, among others, by the signaling pathway of the nuclear factor kappaB (NF-κB) superfamily of proteins, providing an impact on immune system functioning. The present review addresses the influence and role of the NF-κB pathway in the development and progression of most vital endometrial diseases in human and animal species. Immune modulation by NF-κB in endometritis, endometrosis, endometriosis, and carcinoma results in changes in cell migration, proliferation, and inflammation intensity in both the stroma and epithelium. In endometrial cells, the NF-κB signaling pathway may be activated by multiple stimuli, such as bacterial parts, cytokines, or hormones binding to specific receptors. The dysregulation of the immune system in response to NF-κB involves aberrant production of chemokines and cytokines, which plays a role in endometritis, endometriosis, endometrosis, and endometrial carcinoma. However, estrogen and progesterone influence on the reproductive tract always plays a major role in its regulation. Thus, sex hormones cannot be overlooked in endometrial disease physiopathology. While immune system dysregulation seems to be NF-κB-dependent, the hormone-independent and hormone-dependent regulation of NF-κB signaling in the endometrium should be considered in future studies. Future goals in this research should be a step up into clinical trials with compounds affecting NF-κB as treatment for endometrial diseases. Full article
(This article belongs to the Special Issue Role of NF-κB in Carcinogenesis and Its Therapeutic Regulation)
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14 pages, 1158 KiB  
Review
Current Uses of Mushrooms in Cancer Treatment and Their Anticancer Mechanisms
by Hye-Jin Park
Int. J. Mol. Sci. 2022, 23(18), 10502; https://doi.org/10.3390/ijms231810502 - 10 Sep 2022
Cited by 32 | Viewed by 6570
Abstract
Cancer is the leading cause of mortality worldwide. Various chemotherapeutic drugs have been extensively used for cancer treatment. However, current anticancer drugs cause severe side effects and induce resistance. Therefore, the development of novel and effective anticancer agents with minimal or no side [...] Read more.
Cancer is the leading cause of mortality worldwide. Various chemotherapeutic drugs have been extensively used for cancer treatment. However, current anticancer drugs cause severe side effects and induce resistance. Therefore, the development of novel and effective anticancer agents with minimal or no side effects is important. Notably, natural compounds have been highlighted as anticancer drugs. Among them, many researchers have focused on mushrooms that have biological activities, including antitumor activity. The aim of this review is to discuss the anticancer potential of different mushrooms and the underlying molecular mechanisms. We provide information regarding the current clinical status and possible modes of molecular actions of various mushrooms and mushroom-derived compounds. This review will help researchers and clinicians in designing evidence-based preclinical and clinical studies to test the anticancer potential of mushrooms and their active compounds in different types of cancers. Full article
(This article belongs to the Special Issue Role of NF-κB in Carcinogenesis and Its Therapeutic Regulation)
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