NF-κB in Gastric Cancer Development and Therapy
Abstract
:1. Introduction
2. Dysregulation of NF-κB in Gastric Cancer
2.1. NF-κB Signaling
2.2. NF-κB Gene Polymorphisms
2.3. Gene Polymorphisms in NF-κB Signaling Molecules
2.4. Modulation of NF-κB Regulation in Gastric Cancer
3. NF-κB-Regulated Genes and Their Relevance for Gastric Cancer Development
3.1. Immune Response Mediators
3.2. iNOS and COX2
3.3. Effectors in Proliferation, Cell Cycle, Apoptosis, and Invasion
4. Therapeutic Targeting of NF-κB in Gastric Cancer
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
Activator protein 1 | AP1 |
3,3’-diindolylmethane | DIM |
ADP-glycero-β-D-manno-heptose | ADP-hep |
Ataxia-telangiectasia mutated | ATM |
B cell activation factor | BAF |
B-cell lymphoma 2 | Bcl-2 |
Bcl-2-associated X protein | Bax |
Beta-transducin repeat containing E3 ubiquitin protein ligase | β-TrCP |
Cadherin-1 | CDH1 |
Cag pathogenicity island | CagPAI |
Cannabinoid receptor 1 | CNR1 |
Carcinoembryonic antigen-related cell adhesion molecule 19 | CEACAM19 |
Caspase-associated recruitment domains | CARDs |
Chemokine (C-X-C motif) ligand 1 | CXCL1 |
Chemokine (C-X-C motif) ligand 2 | CXCL2 |
Connective tissue growth factor | CTGF |
CXC chemokine receptor 4 | CXCR4 |
CXC chemokine receptor 4 | CXCR4 |
CXC motif chemokine ligand 11 | CXCL11 |
Cyclin-dependent kinase 2 | CDK-2 |
Cyclooxygenase-2 | COX-2 |
Deacetylase sirtuin 1 | SIRT1 |
DNA methyltransferase 3 | DNMT3 |
DNA repair protein | Ku |
Dopamine and cAMP-regulated phosphoprotein 32,000 Da | DARPP-32 |
Epidermal growth factor receptor | EGRF |
Epstein–Barr virus (EBV) latent membrane protein 2 | LMP2A |
Fibroblast growth factor-inducible 14 | FN14 |
Gastric adenocarcinomas | non-cardia GCs |
Gastric cancer | GC |
Gastric mucosa-associated lymphoid tissue | MALT |
Gastroesophageal junction adenocarcinomas | cardia GC |
Gastrokine 1 | GKN1 |
Granulocyte-macrophage colony-stimulating factor | GM-CSF |
Growth-regulated oncogene | GRO-α |
Growth-regulated protein beta | GRO-β |
Growth-regulated protein gamma | GRO-γ |
HOX transcript antisense RNA | HOTAIR |
Human epidermal growth factor receptor 2 | HER2 |
Human telomerase reverse transcriptase | hTERT |
Hypoxia inducible factor 1 alpha | HIF-1α |
Immunohistochemistry | IHC |
Immunohistochemistry analysis | ICH |
Inducible nitric oxide synthase | iNOS, NOS2 |
Inhibitor of growth 4 | ING4 |
Interleukin 1b | IL-1b |
IκB kinase | IKK |
Lipopolysaccharide | LPS |
Lymphotoxin β | LTβ |
Lymphotoxin β | LTβ |
Matrix metallopeptidase 9 | MMP9 |
Mesenchymal stromal cells | MSCs |
Mucosa-associated lymphoid tissue | MALT |
Myeloid differentiation primary response 88 | MyD88 |
NADPH oxidase 1 | NOX1 |
NADPH oxidase organizer 1 | Noxo1 |
NF-κB essential modulator | NEMO |
NF-κB inducing kinase | NIK |
NF-κB1 | p50 |
NF-κB2 | p52 |
Nitric oxide | NO |
Non-cardia gastric adenocarcinoma | NCGC |
Nonsteroidal anti-inflammatory drugs | NSAIDs |
O6-methylguanin-DNA-methyltransferase | MGMT |
Oncogenes latent membrane protein 1 | LMP1 |
Oncoprotein metadherin | MTDH |
Open reading frames | ORFs |
p21-activated kinases | PAKs |
Phosphatase and tensin homolog | PTEN |
Phosphatase of regenerating liver-3 | PRL-3 |
Poly r(C)-binding protein | PCBP |
Programmed death 1 | PD-1 |
Programmed-death ligand 1 | PD-L1 |
Prostaglandin E2 | PGE2 |
Protection of telomeres 1 | POT1 |
Protein alpha-kinase 1 | ALPK1 |
Reactive oxygen species | ROS |
Receptor activator of NF-κB | RANK |
Receptor interacting serine/threonine kinase 2 | RIPK2 |
Rel homology domain | RHD |
Repressor/activator protein 1 | RAP1 |
Sex determining region Y (SRY)-box 2 | SOX2 |
Signal transducers and activators of transcription 3 | STAT3 |
Stress protein metallothionein 2A | MT2A |
T regulatory | Treg |
TNF-induced protein 3-interacting protein 1 | TNIP1 |
Toll-like receptors | TLRs |
TRAF-interacting protein with forkhead-associated domain | TIFA |
Transcription factor nuclear factor kappa B | NF-κB |
Transforming growth factor b kinase 1 | TAK1 |
Trefoil factor 1 | TFF1 |
Tumor necrosis factor receptor-associated factor | TRAF |
Tumor necrosis factor | TNF |
Tumor-associated macrophages | TAMs |
Type IV secretion system | T4SS |
Vascular endothelial growth factor | VEGF |
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Gene Name | Genetic Aberration | Comments | References |
---|---|---|---|
NFKB1 | SNP_rs230521 | observed in GC patients | [32] |
SNP_rs28362491 (−94 ins/del ATTG) | associated with diffuse GC, accelerate severe gastric inflammation | [33,34] | |
SNP_rs4648068 | increased risk of GC | [36,37] | |
homozygous deletion | invasive GC, gastric atrophy in mice | [38,39] | |
NFKB2 | homozygous deletion | gastric hyperplasia, early postnatal death | [40] |
suppressed in gastric mucosal lesions | [39] | ||
NFKBIA | SNP_rs2233408 T/C homozygote | GC susceptibility | [41] |
SNP_rs2233408 T heterozygote | reduced GC risk in intestinal-type non-cardiac GC | ||
SNP_rs17103265 | risk factor for gastric carcinogenesis | [42] | |
SNP_rs696 | cardia GC susceptibility | [43] | |
SNP_rs2233406 | non-cardia GC susceptibility | ||
IΚBKB | SNP_rs2272736 A homozygote | prolonged overall survival time | [44] |
TNIP1 | SNP_rs7708392 | associated with GC risk | [45] |
SNP_rs10036748 | |||
MYD88 | deletion, mutation | gastric mucosal damage, carcinogenesis | [46] |
L265P mutant | observed in gastric mucosa-associated lymphoid tissue (MALT) lymphomas | [47] | |
RIPK2 | SNP_rs16900627 | increased risk of intestinal GC | [48] |
TLR9 | SNP_rs5743836 (−1237 T/C) | associated with H. pylori-induced GC | [49] |
NF-κB Regulated Genes | Comments | References |
---|---|---|
IL-8 | correlates with diffuse-type GC | [87] |
correlates with depth of invasion, venous and lymphatic invasion, low survival rate, enhances cell migration and invasion | [88] | |
IL-17 | positively associates with GC, enhances cell migration and invasion | [67,89] |
IL-1β | promotes gastric dysplasia to GC | [90] |
COX2, MMP9, VEGF | TAMs induce COX2, MMP9, VEGF expression, promote invasion/migration in GC | [91,92,93] |
PD-L1 | relates to a less advanced stage, intestinal type GC | [94] |
associates with poor prognosis for GC patients | [95] | |
NO, PGE2 | potentiates the infiltration of macrophages in stomach tissue, promotes an inflammatory environment | [96,97,98] |
promotes tissue healing via eliminating infectious agents, increasing tissue microcirculation and cell restitution | [99] | |
accelerates turnover of epithelial cells, increasing the mutagenesis rate in inflamed tissue | [100,101,102,103] | |
iNOS, COX-2 | contributes to a gradual progress of gastric carcinogenesis | [104,105,106,107] |
STAT3 | contributes to GC development and progression | [108] |
c-myc, cyclinD1 | high expression in intestinal-type GC | [109] |
HNF4α | HNF4α overexpression correlates with sustained inflammation and GC | [110] |
miR-223-3p, miR-18a-3p, miR-4286 | expression in gastric cancer cells and tissues, links to proliferation and gastric carcinogenesis | [80,111] |
miR-425 | promotes proliferation of GC | [112] |
Noxo1 | associates with gastritis and GC | [113] |
Snail1 | downregulation of E-cadherin in GC tissue | [114] |
hTERT | promotes intestinal metaplasia | [115,116] |
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Chaithongyot, S.; Jantaree, P.; Sokolova, O.; Naumann, M. NF-κB in Gastric Cancer Development and Therapy. Biomedicines 2021, 9, 870. https://doi.org/10.3390/biomedicines9080870
Chaithongyot S, Jantaree P, Sokolova O, Naumann M. NF-κB in Gastric Cancer Development and Therapy. Biomedicines. 2021; 9(8):870. https://doi.org/10.3390/biomedicines9080870
Chicago/Turabian StyleChaithongyot, Supattra, Phatcharida Jantaree, Olga Sokolova, and Michael Naumann. 2021. "NF-κB in Gastric Cancer Development and Therapy" Biomedicines 9, no. 8: 870. https://doi.org/10.3390/biomedicines9080870