biostudies-literatureJi ZHoward Hughes Medical InstituteHHS | NIH | National Cancer InstituteNCI NIH HHS9453-9462https://www.ebi.ac.uk/biostudies/studies/S-EPMC6511065biostudies-literatureUnknown116(19)Using an inducible, inflammatory model of breast cellular transformation, we describe the transcriptional regulatory network mediated by STAT3, NF-κB, and AP-1 factors on a genomic scale. These proinflammatory regulators form transcriptional complexes that directly regulate the expression of hundreds of genes in oncogenic pathways via a positive feedback loop. This transcriptional feedback loop and associated network functions to various extents in many types of cancer cells and patient tumors, and it is the basis for a cancer inflammation index that defines cancer types by functional criteria. We identify a network of noninflammatory genes whose expression is well correlated with the cancer inflammatory index. Conversely, the cancer inflammation index is negatively correlated with the expProceedings of the National Academy of Sciences of the United States of AmericaInflammatory regulatory network mediated by the joint action of NF-kB, STAT3, and AP-1 factors is involved in many human cancers.PMC6511065R01 CA107486K99 CA207865K99 CA 207865CA 107486R00 CA207865Regev AJi ZHe LStruhl KfalseInflammatory regulatory network mediated by the joint action of NF-kB, STAT3, and AP-1 factors is involved in many human cancers.Using an inducible, inflammatory model of breast cellular transformation, we describe the transcriptional regulatory network mediated by STAT3, NF-κB, and AP-1 factors on a genomic scale. These proinflammatory regulators form transcriptional complexes that directly regulate the expression of hundreds of genes in oncogenic pathways via a positive feedback loop. This transcriptional feedback loop and associated network functions to various extents in many types of cancer cells and patient tumors, and it is the basis for a cancer inflammation index that defines cancer types by functional criteria. We identify a network of noninflammatory genes whose expression is well correlated with the cancer inflammatory index. Conversely, the cancer inflammation index is negatively correlated with the exp2019-01-01T00:00:00Z2019 May2026-05-03T06:35:28.417Z2025-06-01T03:26:39.793ZS-EPMC65110653091096010.1073/pnas.1821068116