Role of SNARE proteins in tumourigenesis and their potential as targets for novel anti-cancer therapeutics

• SNAREs regulate cancer cell invasion, chemo-resistance, inflammation and autophagy.
• SNARE co-factors regulate phosphorylation of kinases involved in cancer cell biogenesis.
• SNAREs serve as markers for cancer cells and also promote prosurvival and cell cycle signalling
• SNARE expression is potentially controlled by an oncogene.
• A novel strategy for anti-cancer therapeutics targeting SNAREs is proposed.

The function of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) in cellular trafficking, membrane fusion and vesicle release in synaptic nerve terminals is well characterised. Recent studies suggest that SNAREs are also important in the control of tumourigenesis through the regulation of multiple signalling and transportation pathways. The majority of published studies investigated the effects of knockdown/knockout or overexpression of particular SNAREs on the normal function of cells as well as their dysfunction in tumourigenesis promotion. SNAREs are involved in the regulation of cancer cell invasion, chemo-resistance, the transportation of autocrine and paracrine factors, autophagy, apoptosis and the phosphorylation of kinases essential for cancer cell biogenesis. This evidence highlights SNAREs as potential targets for novel cancer therapy. This is the first review to summarise the expression and role of SNAREs in cancer biology at the cellular level, their interaction with non-SNARE proteins and modulation of cellular signalling cascades. Finally, a strategy is proposed for developing novel anti-cancer therapeutics using targeted delivery of a SNARE-inactivating protease into malignant cells.