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. 2020 Sep 18;27(11):2989–3003. doi: 10.1038/s41418-020-00624-8

Fig. 3. Initiation of necroptosis by cGAS–STING signaling.

Fig. 3

Activation of the cGAS–STING pathway by mitochondrial DNA results in production of IFN and TNF. Binding of IFN to IFNAR1 and TNF to TNFR1 can results in RIPK1–RIPK3 activation, when caspase-8 is inhibited. RIPK1–RIPK3 activates MLKL to execute necroptosis. Moreover, IFN upregulates RIPK3 and MLKL expression. It would be interesting to understand if STING agonists can initiate necroptosis to limit tumor growth when apoptotic caspases are usually inhibited in cancer cells. Green arrow indicate upregulation.