Versatile function of NF-ĸB in inflammation and cancer.

ABSTRACT

Nuclear factor-kappaB (NF-ĸB) plays a crucial role in both innate and adaptive immune systems, significantly influencing various physiological processes such as cell proliferation, migration, differentiation, survival, and stemness. The function of NF-ĸB in cancer progression and response to chemotherapy has gained increasing attention. This review highlights the role of NF-ĸB in inflammation control, biological mechanisms, and therapeutic implications in cancer treatment. NF-ĸB is instrumental in altering the release of inflammatory factors such as TNF-α, IL-6, and IL-1ß, which are key in the regulation of carcinogenesis. Specifically, in conditions including colitis, NF-ĸB upregulation can intensify inflammation, potentially leading to the development of colorectal cancer. Its pivotal role extends to regulating the tumor microenvironment, impacting components such as macrophages, fibroblasts, T cells, and natural killer cells. This regulation influences tumorigenesis and can dampen anti-tumor immune responses. Additionally, NF-ĸB modulates cell death mechanisms, notably by inhibiting apoptosis and ferroptosis. It also has a dual role in stimulating or suppressing autophagy in various cancers. Beyond these functions, NF-ĸB plays a role in controlling cancer stem cells, fostering angiogenesis, increasing metastatic potential through EMT induction, and reducing tumor cell sensitivity to chemotherapy and radiotherapy. Given its oncogenic capabilities, research has focused on natural products and small molecule compounds that can suppress NF-ĸB, offering promising avenues for cancer therapy.