Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer

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• 作者：Denis  ; Drygin  ; ;   ; ^a ;   ; ^{ddrygin@cylenepharma.com} ; Caroline B.  ; Ho¹ ;   ; ^a ; Mayuko  ; Omori^a ; Joshua  ; Bliesath^a ; Chris  ; Proffitt^a ; Rachel  ; Rice² ;   ; ^a ; Adam  ; Siddiqui-Jain^a ; Sean  ; O&rsquo ; Brien^a ; Claire  ; Padgett³ ;   ; ^a ; John K.C.  ; Lim^a ; Kenna  ; Anderes⁴ ;   ; ^a ; William G.  ; Rice^a ; David  ; Ryckman^a
• 关键词：CK2 ; IL-6 ; CX-4945 ; Inflammatory breast cancer
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：11 November 2011
• 年：2011
• 卷：415
• 期：1
• 页码：163-167
• 全文大小：492 K

文摘

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.