Abstract
Gastric cancer is considered one of the most common causes of cancer-related death worldwide and, thus, a major health problem. A variety of environmental factors including physical and chemical noxae, as well as pathogen infections could contribute to the development of gastric cancer. The transcription factor nuclear factor kappa B (NF-κB) and its dysregulation has a major impact on gastric carcinogenesis due to the regulation of cytokines/chemokines, growth factors, anti-apoptotic factors, cell cycle regulators, and metalloproteinases. Changes in NF-κB signaling are directed by genetic alterations in the transcription factors themselves, but also in NF-κB signaling molecules. NF-κB actively participates in the crosstalk of the cells in the tumor micromilieu with divergent effects on the heterogeneous tumor cell and immune cell populations. Thus, the benefits/consequences of therapeutic targeting of NF-κB have to be carefully evaluated. In this review, we address recent knowledge about the mechanisms and consequences of NF-κB dysregulation in gastric cancer development and therapy.
Highlights
Gastric cancer (GC) is highly prevalent among the gastrointestinal cancers and accounts for the third most leading cause of cancer-related mortality worldwide after lung and liver cancers [1]
The pathogenesis and development of GC was correlated to multiple factors, a major risk factor is the infection with Helicobacter pylori, which was classified as class one carcinogen [7,8]
Results from other studies indicate that the activation of NF-κB affects gastric carcinogenesis by promoting the activation of genes involved in cell proliferation, suppression of the apoptosis, metastasis, genomic instability, and drug resistance [23,24]
Summary
Gastric cancer (GC) is highly prevalent among the gastrointestinal cancers and accounts for the third most leading cause of cancer-related mortality worldwide after lung and liver cancers [1]. The majority of GC are non-cardia GCs which can be histologically classified based on Lauren classification into intestinal (gland-like structures) and diffuse types (lacks any glandular structures) [4]. It can be classified clinically as early or advanced GC. The NF-κB family of transcription factors is ubiquitously expressed and plays an essential role in the regulation of a wide variety of biological processes including cell differentiation, proliferation, survival, and, most importantly, immune responses and inflammation [16]. We review NF-κB signaling in gastric carcinogenesis and putative therapeutic strategies
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