Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer |
| |
Authors: | Drygin Denis Ho Caroline B Omori Mayuko Bliesath Joshua Proffitt Chris Rice Rachel Siddiqui-Jain Adam O'Brien Sean Padgett Claire Lim John K C Anderes Kenna Rice William G Ryckman David |
| |
Institution: | aCylene Pharmaceuticals, 5820 Nancy Ridge Dr. Ste 200, San Diego, CA 92121, USA |
| |
Abstract: | Inflammatory breast cancer is driven by pro-angiogenic and pro-inflammatory cytokines. One of them Interleukin-6 (IL-6) is implicated in cancer cell proliferation and survival, and promotes angiogenesis, inflammation and metastasis. While IL-6 has been shown to be upregulated by several oncogenes, the mechanism behind this phenomenon is not well characterized. Here we demonstrate that the pleotropic Serine/Threonine kinase CK2 is implicated in the regulation of IL-6 expression in a model of inflammatory breast cancer. We used siRNAs targeted toward CK2 and a selective small molecule inhibitor of CK2, CX-4945, to inhibit the expression and thus suppress the secretion of IL-6 in in vitro as well as in vivo models. Moreover, we report that in a clinical trial, CX-4945 was able to dramatically reduce IL-6 levels in plasma of an inflammatory breast cancer patient. Our data shed a new light on the regulation of IL-6 expression and position CX-4945 and potentially other inhibitors of CK2, for the treatment of IL-6-driven cancers and possibly other diseases where IL-6 is instrumental, including rheumatoid arthritis. |
| |
Keywords: | CK2 IL-6 CX-4945 Inflammatory breast cancer |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|