Title:At the Crossroads of TNF α Signaling and Cancer
Volume: 17
Author(s): Sonal M. Manohar*
Affiliation:
- Department of Biological Sciences, Sunandan Divatia School of Science, NMIMS (Deemed-to-be) University, Vile Parle (West), Mumbai 400056,
India
Keywords:
TNFalpha, Cancer, NF-kappa B, Apoptosis, Proliferation, Necroptosis.
Abstract: Tumor necrosis factor-alpha (TNFα) is a pleiotropic pro-inflammatory cytokine of the TNF superfamily. It regulates key cellular processes such as
death, and proliferation besides its well-known role in immune response through activation of various intracellular signaling pathways (such as
MAPK, Akt, NF-κB, etc.) via complex formation by ligand-activated TNFα receptors. TNFα tightly regulates the activity of key signaling proteins
via their phosphorylation and/or ubiquitination which culminate in specific cellular responses. Deregulated TNFα signaling is implicated in
inflammatory diseases, neurological disorders, and cancer. TNFα has been shown to exert opposite effects on cancer cells since it activates prosurvival
as well as anti-survival pathways depending on various contexts such as cell type, concentration, cell density, etc. A detailed
understanding of TNFα signaling phenomena is crucial for understanding its pleiotropic role in malignancies and its potential as a drug target or an
anticancer therapeutic. This review enlightens complex cellular signaling pathways activated by TNFα and further discusses its role in various
cancers.