Augusta University
Allison BrownThis work has gained national publicity, as indicated by the following reports:
[Kim G, Ouzounova M, Quraishi AA, Davis A, Tawakkol N, Clouthier SG, Malik F, Paulson AK, D’Angelo RC, Korkaya S, Baker TL, Esen ES, Prat A, Liu S, Kleer CG, Thomas DG, Wicha MS, Korkaya H. SOCS3-mediated regulation of inflammatory cytokines in PTEN and p53 inactivated triple negative breast cancer model.Oncogene. 2014 Feb 17. doi: 10.1038/onc.2014.4. [Epub ahead of print]]
Triple negative breast cancer (TNBC) is an aggressive cancer that has notoriously been difficult to treat. It lacks three types of receptor proteins that have been therapeutically targeted in treating other types of breast cancer. Since these receptors are not causing the cancer in TNBC, those receptor-targeting treatment strategies are not particularly effective. So Dr. Korkaya, of GRU Cancer Center’s Molecular Oncology Biomarkers Program, and colleagues took a different approach.
As in many cancers, tumor suppressor proteins p53 and PTEN, which negatively regulate stem cell growth, are inactivated in tumors of the breast. Dr. Korkaya’s team found that genetically “knocking down” p53 and PTEN expression in laboratory models activated the pro-inflammatory IL6/Stat3/NFkB signaling cascade, leading to increased metastatic cancer stem cells and tumor growth. The genetic profile of these tumors corresponded to that of the “claudin-low” TNBC subtype.
Although pro-inflammatory IL6 signaling is typically shut off by a co-produced protein called SOCS3, the expression of SOCS3 is low in “claudin-low” tumors. The researchers discovered that inducing SOCS3 expression – or blocking IL-6 signaling – led to reduction of the cancer stem cell population, tumor growth, and metastasis in mouse models.
In addition to revealing key attributes of inflammatory signaling in cancer, this research, published in Oncogene, identified IL-6 inhibition as a new approach to the treatment of the “claudin-low” TNBC subtype. These results are particularly exciting since IL-6 inhibitors are currently approved for clinical use in treating other inflammation-related diseases, which could expedite future clinical trials.
