Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer.
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.
Cylene Pharmaceuticals, 5820 Nancy Ridge Dr. Ste 200, San Diego, CA 92121, USA. ddrygin@cylenepharma.com
Denis
D
Drygin
Caroline B
CB
Ho
Mayuko
M
Omori
Joshua
J
Bliesath
Chris
C
Proffitt
Rachel
R
Rice
Adam
A
Siddiqui-Jain
Sean
S
O'Brien
Claire
C
Padgett
John K C
JK
Lim
Kenna
K
Anderes
William G
WG
Rice
David
D
Ryckman
D000818:Animals; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009287:Naphthyridines / Q000627:therapeutic use; D010619:Phenazines; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D047390:Casein Kinase II; D015850:Interleukin-6; D009287:Naphthyridines; D010619:Phenazines; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D000093242:Interleukin-6 Inhibitors; C494086:STAT3 protein, human; C555142:silmitasertib