Fig. 6: AKT and EZH2 inhibitors trigger involution-related cytokine production by cooperatively activating STING–TBK1 signalling.
From: AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution
a, The relative change in the cell numbers for cells that were transfected with siControl or siIL-6R and treated with the indicated drugs. b, The relative change in BMF expression (RT–qPCR) in SUM149PT cells transfected with siControl or siIL-6R and treated with the indicated drugs. c, Immunoblot analysis of SUM149PT cells transfected with siRNA against IL6R or a control sequence and then treated with vehicle or EZH2/AKTi. d, The relative cell numbers in MDA-MB-468 cells transduced with sgControl or sgSTING (left) or treated with TBK1i (right). e, The amount of IL-6 (ELISA) relative to the DMSO treatment group in the indicated arms after 8 h. f, Immunoprecipitation (IP) of STING or IgG control in MDA-MB-468 cells treated with the indicated drugs for 8 h followed by immunoblotting using the indicated antibodies. g, Immunoblot analysis of MDA-MB-468 cells that were treated with EZH2i and/or AKTi using the indicated antibodies. h, Live-cell imaging of SUM159PT cells (resistant) transduced with GFP or GATA3 overexpression constructs treated with EZH2/AKTi and/or STING agonist ADUS100 (STINGag). i, The mechanism of action of combined EZH2 and AKT inhibitors to induce cell death and tumour regression in TNBC. The diagram was created using BioRender. For all panels, data are mean ± s.d. of biologically independent samples. All panels showing immunoblots were repeated at least three times. For all experiments, n = 3. P values were calculated using unpaired one-tailed heteroscedastic Student’s t-tests.
