Fig. 5

Rhamm-loss blunts response to STING-activated interferon signaling. A Py1189 MMTV-PyMT tumor cells were exposed to the mouse STING agonist, MDXAA, and the effect on tumor cell survival was quantified with AlamarBlue as described in Methods. MDXAA reduces the survival of Rhamm^+/+ Py1189 tumor cells but has no significant effect when Rhamm is knocked down. Values are the Median and SD, n = 8 replicates. **p < 0.01, ****p < 0.00001, ******p < 0.000001. B STAT1 activity in the STING agonist, G10-stimulated RHAMM^+/+ and RHAMM^−/− MDA-MB-231 tumor cells were measured by quantifying nuclear STAT1 protein as described in Methods. Results show that RHAMM-loss significantly reduces STAT1 activity. Values are the median and SD. n = 30 cells/genotype. ****p < 0.0001. C, D RHAMM^+/+ and RHAMM^−/− MDA-MB-231 tumor cells were exposed to the human STING agonist G10, and survival was quantified using AlamarBlue (C) and cleaved Casapse3 (D) as described in Methods. Results show that similar to the MMTV-PyMT tumor cells, RHAMM-loss in MDA-MB-231 cells generates resistance to G10-induced cell death. Values are the Median and Std. Dev. n = 6 replicates. *p < 0.05, **p < 0.01