Inflammatory regulatory network mediated by the joint action of NF-kB, STAT3, and AP-1 factors is involved in many human cancers
MetadataShow full item record
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 expression of genes involved in DNA metabolism, and transformation is associated with genome instability. We identify drugs whose efficacy in cell lines is correlated with the cancer inflammation index, suggesting the possibility of using this index for personalized cancer therapy. Inflammatory tumors are preferentially associated with infiltrating immune cells that might be recruited to the site of the tumor via inflammatory molecules produced by the cancer cells.
DepartmentMassachusetts Institute of Technology. Department of Biology; Koch Institute for Integrative Cancer Research at MIT
Proceedings of the National Academy of Sciences of the United States of America
Proceedings of the National Academy of Sciences
Ji, Zhe et al. “Inflammatory regulatory network mediated by the joint action of NF-kB, STAT3, and AP-1 factors is involved in many human cancers.” Proceedings of the National Academy of Sciences of the United States of America 116 (2019): 9453-9462 © 2019 The Author(s)
Final published version