scholarly journals Reduced microRNA-218 expression is associated with high nuclear factor kappa B activation in gastric cancer

Cancer ◽  
2009 ◽  
pp. NA-NA ◽  
Author(s):  
Caiping Gao ◽  
Zhiyu Zhang ◽  
Wenzhong Liu ◽  
Shudong Xiao ◽  
Weiqi Gu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa

scholarly journals A Positive Feedback Loop Between Gastric Cancer Cells and Tumor-associated Macrophage Induces Malignancy Progression

2022 ◽  
Author(s):  
Haiyan Piao ◽  
Lingfeng Fu ◽  
Yang Liu ◽  
Yue Wang ◽  
Xiangyu Meng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Nuclear Factor Kappa B ◽  
Luciferase Reporter ◽  
Nuclear Factor ◽  
Positive Feedback Loop ◽  
Nuclear Factor Kappa

Abstract Background: Hypoxia and inflammation tumor microenvironment (TME) play a crucial role in tumor development and progression. Although increased understanding of TME contributed to gastric cancer (GC) progression and prognosis, the direct interaction between macrophage and GC cells was not fully understood.Methods: Hypoxia and normoxia macrophage microarrays of GEO database was analyzed. The peripheral blood mononuclear cell acquired from the healthy volunteers. The expression of CXCL8 in GC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR), western-blot, Elisa and immunofluorescence. Cell proliferation, migration, and invasion were evaluated by cell counting kit 8 (CCK8), colony formation, real-time imaging of cell migration and transwell. Luciferase reporter assays and chromatin immunoprecipitation were used to identify the interaction between transcription factor and target gene. Especially, a series of truncated and mutation reporter genes were applied to identify precise binding sites.The corresponding functions were verified in the complementation test and in vivo animal experiment.Results: Our results revealed that Hypoxia triggered macrophage secreted C-X-C Motif Chemokine Ligand 8 (CXCL8), which induced GC invasion and proliferation. This macrophage-induced GC progression was CXCL8 activated C-X-C Motif Chemokine Receptor 1/2 (CXCR1/2) on the GC cell membrane subsequently hyperactivated Janus kinase 1/ Signal transducer and activator of transcription 1 (JAK/STAT1) signaling pathway. Then, the transcription factor STAT1 directly led to the overexpression and secretion of Interleukin 10 (IL-10). Correspondingly, IL-10 induced the M2-type polarization of macrophages through the Nuclear Factor kappa B (NF-κB) pathway-dependent mechanism and continued to increase the expression and secretion of CXCL8 through the transcription factor Nuclear Factor Kappa B Subunit 1 (NFKB1, p50). It suggested a positive feedback loop between macrophage and GC. In clinical GC samples, increased CXCL8 predicted a patient's pessimistic outcome.Conclusion: Our work identified a positive feedback loop governing cancer cells and macrophage in GC that contributed to tumor progression and patient outcome.

scholarly journals Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products

2013 ◽  
Vol 92 (3) ◽  
pp. 267-276 ◽  
Author(s):  
Kanjoormana A. Manu ◽  
Muthu K. Shanmugam ◽  
Feng Li ◽  
Luxi Chen ◽  
Kodappully Sivaraman Siveen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Nude Mice ◽  
Nuclear Factor Kappa B ◽  
Human Gastric Cancer ◽  
Nuclear Factor ◽  
Gene Products ◽  
Nuclear Factor Kappa ◽  
Gastric Cancer Xenograft
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