NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

Sepideh Mirzaei; Sam Saghari; Farzaneh Bassiri; Rasoul Raesi; Ali Zarrabi; Kiavash Hushmandi; Gautam Sethi; Vinay Tergaonkar

doi:10.1002/jcp.30759

journal article May 13, 2022

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

Sepideh Mirzaei Sam Saghari Farzaneh Bassiri Rasoul Raesi Ali Zarrabi

Kiavash Hushmandi Gautam Sethi

Vinay Tergaonkar

Journal of Cellular Physiology Vol. 237 No. 7 pp. 2770-2795 · Wiley

View at Publisher Save 10.1002/jcp.30759

Abstract

AbstractMetastasis 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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Details

Published: May 13, 2022
Vol/Issue: 237(7)
Pages: 2770-2795
License: View

Authors

S

Sepideh Mirzaei

Department of Biology, Faculty of Science, Science and Research Branch Islamic Azad University Tehran Iran

S

Sam Saghari

Department of Health Services Management, Tehran Medical Sciences Islamic Azad University Tehran Iran

F

Farzaneh Bassiri

Department of Biology, Fars Science and Research Branch Islamic Azad University Fars Iran; Department of Biology, Shiraz Branch Islamic Azad University Shiraz Iran

R

Rasoul Raesi

PhD in Health Services Management Mashhad University of Medical Sciences Mashhad Iran

A

Ali Zarrabi

Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences Istinye University Istanbul Turkey

K

Kiavash Hushmandi

Department of Food Hygiene and Quality Control, Division of Epidemiology and Zoonoses, Faculty of Veterinary Medicine University of Tehran Tehran Iran

G

Gautam Sethi

Department of Pharmacology, Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore; Yong Loo Lin School of Medicine, NUS Centre for Cancer Research (N2CR) National University of Singapore Singapore Singapore

V

Vinay Tergaonkar

Laboratory of NF‐κB Signaling Institute of Molecular and Cell Biology (IMCB), 61 Biopolis Drive, Proteos Singapore Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore

Cite This Article

Sepideh Mirzaei, Sam Saghari, Farzaneh Bassiri, et al. (2022). NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition. Journal of Cellular Physiology, 237(7), 2770-2795. https://doi.org/10.1002/jcp.30759

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

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