NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition
Abstract
Metastasis of tumor cells is a complex challenge and significantly diminishes the overall survival and prognosis of cancer patients. The epithelial‐to‐mesenchymal transition (EMT) is a well‐known mechanism responsible for the invasiveness of tumor cells. A number of molecular pathways can regulate the EMT mechanism in cancer cells and nuclear factor‐kappaB (NF‐κB) is one of them. The nuclear translocation of NF‐κB p65 can induce the transcription of several genes involved in EMT induction. The present review describes NF‐κB and EMT interaction in cancer cells and their association in cancer progression. Due to the oncogenic role NF‐κB signaling, its activation enhances metastasis of tumor cells via EMT induction. This has been confirmed in various cancers including brain, breast, lung and gastric cancers, among others. The ZEB1/2, transforming growth factor‐β, and Slug as inducers of EMT undergo upregulation by NF‐κB to promote metastasis of tumor cells. After EMT induction driven by NF‐κB, a significant decrease occurs in E‐cadherin levels, while N‐cadherin and vimentin levels undergo an increase. The noncoding RNAs can potentially also function as upstream mediators and modulate NF‐κB/EMT axis in cancers. Moreover, NF‐κB/EMT axis is involved in mediating drug resistance in tumor cells. Thus, suppressing NF‐κB/EMT axis can also promote the sensitivity of cancer cells to chemotherapeutic agents.
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NF-κB is a pivotal transcription factor implicated in MM pathogenesis, particularly in the bone marrow microenvironment.
“NF-κB is a pivotal transcription factor implicated in MM pathogenesis, particularly in the bone marrow microenvironment.”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [137]
NF-κB is activated by various stimuli, including TLR4 ligands and cytokines such as CD40, TNF-α, IL-1β, and BAFF within the bone marrow microenvironment.
“NF-κB is activated by various stimuli, including Toll-like receptor 4 (TLR4) ligands and cytokines such as CD40, TNF-α, IL-1β, and B-cell activating factor (BAFF) within the bone marrow microenvironment.”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [137]
NF-κB signaling is categorized into canonical and non-canonical pathways; the canonical pathway involves p50-RelA complexes regulated by IKKα, β, and γ, while the non-canonical pathway involves p52-RelB complexes regulated by IKKα.
“NF-κB signaling is categorized into canonical and non-canonical pathways. In the canonical pathway, NF-κB1 (p50)-RelA (p65) complexes are activated and regulated by a trimeric complex consisting of IκB kinases (IKK) α, β, and γ. Conversely, the non-canonical pathway involves NF-κB2 (p52)-RelB complexes, regulated by a dimeric complex of IKKα [136, 137] (Fig. 1).”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [137]
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Beyond IκBs: alternative regulation of NF‐KB activity
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Multiple myeloma: signaling pathways and targeted therapy
Lu, Q., Yang, D., Li, H., Niu, T., & Tong, A. (2024) · Molecular biomedicine · doi:10.1186/s43556-024-00188-w · Cited by 90 · see citing works
Role of NF-κB Signaling in the Interplay between Multiple Myeloma and Mesenchymal Stromal Cells
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- Authors
- Mirzaei, S., Saghari, S., Bassiri, F., Raesi, R., Zarrabi, A., Hushmandi, K., Sethi, G., & Tergaonkar, V.
- Affiliations
- Islamic Azad University, Tehran (IR)
- Islamic Azad University, Science and Research Branch (IR)
- Mashhad University of Medical Sciences (IR)
- Istinye University (TR)
- University of Tehran (IR)
- National University of Singapore (SG)
- Corresponding author
- Hushmandi, Kiavash
- Sethi, Gautam
- Tergaonkar, Vinay
- ORCID
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2022-05-13
- Volume
- 237
- Issue
- 7
- Pages
- 2770-2795
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- OpenAlex
- W4280544607
- Cited by
- 243
- References
- 3
- Citations by year
- 2026: 33 · 2025: 69 · 2024: 81 · 2023: 42 · 2022: 18
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- NF-κB, epithelial-mesenchymal transition, metastasis, p65 nuclear translocation, ZEB1/2, TGF-beta, Slug, E-cadherin, N-cadherin, vimentin, non-coding RNA, drug resistance, chemosensitivity, tumor progression
- MeSH terms
- Animals, Humans, Neoplasms, Signal Transduction, Transforming Growth Factor beta, NF-kappa B, Cell Line, Tumor, Epithelial-Mesenchymal Transition
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