Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis

被引:330
作者
Ancrile, Brooke [1 ]
Lim, Kian-Huat [1 ]
Counter, Christopher M. [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Dept Radiat Oncol, Durham, NC 27710 USA
关键词
Ras; oncogene; IL6; cytokine; cancer;
D O I
10.1101/gad.1549407
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ras is mutated to remain in the active oncogenic state in many cancers. As Ras has proven difficult to target therapeutically, we searched for secreted, druggable proteins induced by Ras that are required for tumorigenesis. We found that Ras induces the secretion of cytokine IL6 in different cell types, and that knockdown of IL6, genetic ablation of the IL6 gene, or treatment with a neutralizing IL6 antibody retard Ras-driven tumorigenesis. IL6 appears to act in a paracrine fashion to promote angiogenesis and tumor growth. Inhibiting IL6 may therefore have therapeutic utility for treatment of cancers characterized by oncogenic Ras mutations.
引用
收藏
页码:1714 / 1719
页数:6
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