Cancer-associated pathways influenced by SIS ECM in CT26 spheroids were driven by an upregulation in 2’−5’ oligoadenylate synthetases 2 and 3 (Oas2, Oas3) (Supplementary Fig. 6d) also associate with immune regulation, which are enzymes activated by IFN signaling cascades and has been shown to establish an immunosuppressive microenvironment46. Here, OAS3 is linked to cancer.