sahar eskandari,1,*
1. .Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Introduction: Introduction and aim: NF-B-mediated signaling pathways play a direct role in preserving cancer stem cell traits linked to tumor growth. An NF-B-dependent pathway may be responsible for the spread of cancer. Another significant characteristic of cancer cell is their lack of apoptosis and overexpression of ABC genes, which is associated with their resistance to cytostatic medications. Numerous signaling pathways, such as Notch, Sonic hedgehog (Shh), and wingless-type, are in theory linked to control of their self-replacement (Wnt). Investigating the role of the NF-ĸB signaling pathway in cancer was the goal of this study .
Methods: Search Method: This study was investigated the Importance of the NF-ĸB signaling pathway in cancer and based on reliable scientific databases such as Science Direct, Springer, Google Scholar, and PubMed.
Results: Results: The findings demonstrated that NF-B is widely expressed and mediates a variety of biological activities, including immunology, cell proliferation, inflammation, memory, and learning. The DNA-binding and dimerization functions of the NF-B family's members depend on a conserved n-terminal REL homology domain (RHD). These family members particularly include the five subunits of NF-κB, namely RELA (p65), RELB, c-REL, p50, and p52, and the NF-κB. The NF-κB subunits RELA, RELB, and c-REL additionally comprise a C-terminal transactivation domain (TAD). The IKK complex (IKK/IKK/IKK) is phosphorylated by the binding of ligands to their corresponding receptors (such as CD40) in a way that is dependent on C-IAP, TRAF2/3, and NIK (NF-B-inducing kinase). In turn, phosphorylated IKKs phosphorylate IB, which is then degraded by the proteasome and has its NLS unmasked within the p50/p65 NF-B dimer. The NF-B dimer is then translocated into the nucleus where it binds to specific target sites and triggers the production of the target gene. In contrast to this canonical NF-B signaling cascade, non-canonical NF-B signaling is mediated by the phosphorylation of IKKs via NIK, which in turn causes p100 to be phosphorylated before being processed by the proteasome to become p52. Binding to particular NF-B sites and the subsequent nuclear translocation of the p52/RELB NF-B dimer are followed by the activation of particular target genes. Due to its diverse physiological roles and target genes, the dysregulation of canonical and non-canonical NF-B signaling pathways is directly linked to a number of characteristics of cancerogenesis and cancer development. Specifically, epithelial-to-mesenchymal transition (EMT), angiogenesis, invasiveness, and metastasis are all crucial tumor-promoting mechanisms that are mediated by canonical NF-B signaling. Cell proliferation is also stimulated, and apoptosis, the EMT, invasiveness, and metastasis are all prevented. In a wide variety of malignancies from different organs, NF-B was revealed to be constitutively active as a driver of such critical mechanisms initiating and propagating tumor growth. Additionally, numerous oncogenic mutations or a protracted, chronic inflammatory milieu might cause the NF-B subunits to become constitutively active. It has been demonstrated that persistent inflammation, which is brought on by elevated NF-B activity, promotes the development of a protumor genic microenvironment in colon cancer. However, NF-B has also been implicated in anti-inflammatory functions that have a direct impact on tumor development and treatment resistance. For instance, it has been observed that overexpression of the NF-B p50 homodimer in M1 macrophages associated with tumors inhibits inflammatory and antitumor responses in mouse fibrosarcoma. The NF-B p50 homodimer was also activated in human ovarian carcinomas with abnormal tumor-associated macrophage response to M1 activation signals, suggesting a context-dependent role for NF-B activity at least in malignancies linked to chronic inflammation.
Conclusion: Conclusion: In conclusion, there is strong proof that NF-B plays a crucial role in organ-specific malignancies. Despite the fact that cancer stem cells were discovered in 1994, the study of NF-function B's in tumor-initiating cancer stem cells is still in its infancy. Although surface markers are limited in their capacity to target cancer in terms of marker specificity, the NF-B family and the signaling pathways they mediate for both apoptosis and self-renewal may offer a viable target for therapeutic interventions.