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

被引:150
|
作者
Mirzaei, Sepideh [1 ]
Saghari, Sam [2 ]
Bassiri, Farzaneh [3 ,4 ]
Raesi, Rasoul [5 ]
Zarrabi, Ali [6 ]
Hushmandi, Kiavash [7 ]
Sethi, Gautam [8 ,9 ]
Tergaonkar, Vinay [10 ,11 ]
机构
[1] Islamic Azad Univ, Fac Sci, Dept Biol, Sci & Res Branch, Tehran, Iran
[2] Islamic Azad Univ, Dept Hlth Serv Management, Tehran Med Sci, Tehran, Iran
[3] Islamic Azad Univ, Dept Biol, Fars Sci & Res Branch, Fars, Iran
[4] Islamic Azad Univ, Dept Biol, Shiraz Branch, Shiraz, Iran
[5] Mashhad Univ Med Sci, PhD Hlth Serv Management, Mashhad, Razavi Khorasan, Iran
[6] Istinye Univ, Fac Engn & Nat Sci, Dept Biomed Engn, Istanbul, Turkey
[7] Univ Tehran, Fac Vet Med, Div Epidemiol & Zoonoses, Dept Food Hyg & Qual Control, Tehran 1417466191, Iran
[8] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117600, Singapore
[9] Natl Univ Singapore, NUS Ctr Canc Res N2CR, Yong Loo Lin Sch Med, Singapore, Singapore
[10] Inst Mol & Cell Biol IMCB, Lab NF KB Signaling, 61 Biopolis Dr, Singapore 138673, Singapore
[11] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore, Singapore
关键词
cancer therapy; chemoresistance; EMT; metastasis; NF-kappa B signaling; XENOGRAFT MOUSE MODEL; HUMAN GASTRIC-CANCER; HEPATOCELLULAR-CARCINOMA CELLS; STAT3 SIGNALING CASCADE; CARCINOGENESIS IN-VITRO; LONG NONCODING RNAS; BREAST-CANCER; STEM-CELLS; NASOPHARYNGEAL CARCINOMA; COLORECTAL-CANCER;
D O I
10.1002/jcp.30759
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-kappa B) is one of them. The nuclear translocation of NF-kappa B p65 can induce the transcription of several genes involved in EMT induction. The present review describes NF-kappa B and EMT interaction in cancer cells and their association in cancer progression. Due to the oncogenic role NF-kappa B 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-beta, and Slug as inducers of EMT undergo upregulation by NE-kappa B to promote metastasis of tumor cells. After EMT induction driven by NF-kappa B, 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-kappa B/EMT axis in cancers. Moreover, NF-kappa B/EMT axis is involved in mediating drug resistance in tumor cells. Thus, suppressing NF-kappa B/EMT axis can also promote the sensitivity of cancer cells to chemotherapeutic agents.
引用
收藏
页码:2770 / 2795
页数:26
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