NF-?B as a regulator of cancer metastasis and therapy response: A focus on epithelial-mesenchymal transition

Özet

Metastasis of tumor cells is a complex challenge and significantly diminishes theoverall survival and prognosis of cancer patients. The epithelial?to?mesenchymaltransition (EMT) is a well?known mechanism responsible for the invasiveness oftumor cells. A number of molecular pathways can regulate the EMT mechanism incancer cells and nuclear factor?kappaB (NF??B) is one of them. The nucleartranslocation of NF??B p65 can induce the transcription of several genes involved inEMT induction. The present review describes NF??B and EMT interaction in cancercells and their association in cancer progression. Due to the oncogenic role NF??Bsignaling, its activation enhances metastasis of tumor cells via EMT induction. Thishas been confirmed in various cancers including brain, breast, lung and gastriccancers, among others. The ZEB1/2, transforming growth factor??, and Slug asinducers of EMT undergo upregulation by NF??B to promote metastasis of tumorcells. After EMT induction driven by NF??B, a significant decrease occurs inE?cadherin levels, while N?cadherin and vimentin levels undergo an increase. Thenoncoding RNAs can potentially also function as upstream mediators and modulateNF??B/EMT axis in cancers. Moreover, NF??B/EMT axis is involved in mediatingJ Cell Physiol. 2022;1–26.wileyonlinelibrary.com/journal/jcp© 2022 Wiley Periodicals LLC.|1Abbreviations:AREG, amphiregulin; circRNA, circular RNA; DLC?1, deleted in liver cancer?1; EMT, epithelial?to?mesenchymal transition; EMT?TFs, EMT?inducing transcription factors;FABP5, fatty acid?binding protein 5; GH, growth hormone; IGF1R, insulin like growth factor?1 receptor; IKK, I?B kinase; IL, interleukin; lncRNA, long noncoding RNA; MANF, mesencephalicastrocyte?derived neutrophic factor; miRNA, microRNA; NF??B, nuclear factor?kappaB; NIK, NF??B inducing kinase; SIRTs, sirtuins; SMC4, structural maintenance of chromosome 4;STAT3, signal transducer and activator of transcription 3; TGF??, transforming growth factor??; TLR?4, toll like growth factor?4; TNF, tumor necrosis factor. drug resistance in tumor cells. Thus, suppressing NF??B/EMT axis can also promotethe sensitivity of cancer cells to chemotherapeutic agents

Açıklama

Anahtar Kelimeler

Cancer Therapy, Chemoresistance, EMT, Metastasis, NF‐κB, Signaling

Kaynak

Journal of Cellular physicology

WoS Q Değeri

Q1

Scopus Q Değeri

N/A

Cilt

Sayı

Künye

Mirzaei S, Saghari S, Bassiri F, Raesi R, Zarrabi A, Hushmandi K, Sethi G, Tergaonkar V. NF-κB as a regulator of cancer metastasis and therapy response: A focus on epithelial-mesenchymal transition. J Cell Physiol. 2022 May 13. doi: 10.1002/jcp.30759. Epub ahead of print. PMID: 35561232