Fig. 8.

Proposed model of cisplatin toxicity in non-tumour cells. In canonical SG formation, stress causes the inhibition of translation initiation, polysome disassembly and SG formation. SGs sequester RACK1 and DDX3X, preventing their participation in their respective signalling pathways, promoting cell survival. In cisplatin-induced SG formation, cisplatin localises to SGs, either by directly binding to SGs or by binding with VCP and HSP90. This accumulation of cisplatin at SGs impairs their assembly, alters their composition and affects their persistence. These Cis-SGs have greatly reduced sequestration of signalling proteins RACK1 and DDX3X. These signalling molecules are therefore available to participate in their respective signalling pathways, resulting in the induction of pyroptosis and/or apoptosis.