Transcriptional Regulation during Aberrant Activation of NF-κB Signalling in Cancer

• Published in: Cells (Basel, Switzerland) Vol. 12; no. 5; p. 788
• Main Authors: Deka, Kamalakshi, Li, Yinghui
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-03-2023; MDPI
• Subjects: Cancer; Cellular signal transduction; Chromatin; chromatin landscape; Cytokines; Development and progression; epigenetic; Epigenetics; Gene expression; Gene Expression Regulation; Gene regulation; Genetic aspects; Genetic regulation; Genetic transcription; Health aspects; Humans; Inflammation; Inflammation - metabolism; Innate immunity; Kinases; Macromolecules; Malignancy; Microenvironments; Neoplasms; NF-kappa B - metabolism; NF-κB protein; NF-κB signalling; Phosphorylation; Proteins; Review; Signal transduction; Signal Transduction - genetics; Transcription factors; Tumor Microenvironment; Tumor necrosis factor-TNF; Tumors; Singapore; chromatin landscape; cancer; epigenetic; NF-κB signalling
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12050788

The NF-κB signalling pathway is a major signalling cascade involved in the regulation of inflammation and innate immunity. It is also increasingly recognised as a crucial player in many steps of cancer initiation and progression. The five members of the NF-κB family of transcription factors are activated through two major signalling pathways, the canonical and non-canonical pathways. The canonical NF-κB pathway is prevalently activated in various human malignancies as well as inflammation-related disease conditions. Meanwhile, the significance of non-canonical NF-κB pathway in disease pathogenesis is also increasingly recognized in recent studies. In this review, we discuss the double-edged role of the NF-κB pathway in inflammation and cancer, which depends on the severity and extent of the inflammatory response. We also discuss the intrinsic factors, including selected driver mutations, and extrinsic factors, such as tumour microenvironment and epigenetic modifiers, driving aberrant activation of NF-κB in multiple cancer types. We further provide insights into the importance of the interaction of NF-κB pathway components with various macromolecules to its role in transcriptional regulation in cancer. Finally, we provide a perspective on the potential role of aberrant NF-κB activation in altering the chromatin landscape to support oncogenic development.