The Role Of NF-κB Signaling Pathway In Cell Proliferation And Anti-apoptosis As Well As Its Blockade Strategies In ESCC Cells

Aberrant activation of cell signaling pathway has been associated with proliferation, inhibitory apoptosis, invasive growth and metastasis of tumor cells as well as their elevated resistants to radiation and chemotherapy. Some studies have shown that NF-κB signaling pathway might be a new target for therapeutic strategies in cancers due to its role in carcinogenesis and development.NF-κB is activated in many human tumors. The NF-κB/Rei family can form various homo- or hetero-dimers. However, the most studied form is a heterodimer of the p50 and p65 subunits predominant in many kinds of cells. In most normal cells, NF-κB is sequestered in an inactive form through its tight association with the cytoplasmic inhibitor proteins, called inhibitors of NF-κB (IκB), which is catalyzed by an IκB kinase (IKK). A variety of extracellular stimulus factors such as TNF-α, IL-1, radiation and some chemotherapeutic drugs trigger a common signal transduction pathway based on the phosphorylation and degradation of IκB to freely active NF-κB. The released activated NF-κB is rapidly translocated to the nucleus and binds to the promoter region in the relevant downstream genes to touch off a series of transcriptional events.Constitutively activated NF-κB has been implicated in survival, adherence, transformation and proliferation of tumor cells. Activation of NF-κB has been...