Tumor necrosis factor and cancer, buddies or foes?

Abstract

Tumor necrosis factor (TNF) is a multifunctional cytokine that plays important roles in diverse cellular events such as cell survival, proliferation, differentiation, and death. As a pro-inflammatory cytokine, TNF is secreted by inflammatory cells, which may be involved in inflammation-associated carcinogenesis. TNF exerts its biological functions through activating distinct signaling pathways such as nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK). NF-κB is a major cell survival signal that is anti-apoptotic, whereas sustained JNK activation contributes to cell death. The crosstalk between the NF-κB and JNK is involved in determining cellular outcomes in response to TNF. In regard to cancer, TNF is a double-dealer. On one hand, TNF could be an endogenous tumor promoter, because TNF stimulates the growth, proliferation, invasion and metastasis, and tumor angiogenesis of cancer cells. On the other hand, TNF could be a cancer killer. The property of TNF in inducing cancer cell death renders it a potential cancer therapeutic, although much work is needed to reduce its toxicity for systematic TNF administration. Recent studies have focused on sensitizing cancer cells to TNF-induced apoptosis through inhibiting survival signals such as NF-κB, by combined therapy. In this article we provide an overview of the roles of TNF-induced signaling pathways in cancer biology with specific emphasis on carcinogenesis and cancer therapy.

A novel role for TNFAIP2: its correlation with invasion and metastasis in nasopharyngeal carcinoma

“…[35][36][37] Furthermore, VEGF expression was found to be markedly increased and correlated with microvessel density in nasopharyngeal carcinoma patients. 30 Similarly, we herein found that TNFAIP2 is a downstream target of TNFa that acts as a potential angiogenic factor, as shown by the association of its expression with microvessel density in vivo.…”

Gambogic acid inhibits TNF-α-induced invasion of human prostate cancer PC3 cells in vitro through PI3K/Akt and NF-κB signaling pathways

“…High doses of human recombinant TNF-α were found to exert a powerful anti-cancer effect by inducing cell apoptosis and inhibiting tumor blood vessel formation. However, in low doses and with chronic stimulation, TNF-α could induce angiogenesis, proliferation, invasion and metastasis of tumor cells [2] .…”

TNFα-Induced Necroptosis and Autophagy via Supression of the p38–NF-κB Survival Pathway in L929 Cells

“…Tumor necrosis factor alpha (TNFα), a pleiotropic cytokine, mediates a broad range of proinflammatory activities, cell proliferation, differentiation and death (12,13). After stimulation with TNFα, three pathways can be initiated (14 -16).…”