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

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.