Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis
Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis
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DOI：
10.1101/gad.1549407
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发表时间：
2007-07-15
影响因子：
10.5
通讯作者：
Counter, Christopher M.
中科院分区：
文献类型：
--
作者：
Ancrile, Brooke;Lim, Kian-Huat;Counter, Christopher M.
Ras在许多癌症中突变以保持活性致癌状态。由于Ras已被证明难以在治疗上靶向，我们寻找由Ras诱导的肿瘤发生所需的分泌的、可药物化的蛋白。我们发现Ras在不同的细胞类型中诱导细胞因子IL 6的分泌，并且IL 6的敲除、IL 6基因的基因消融或用中和IL 6抗体的治疗延迟Ras驱动的肿瘤发生。IL 6似乎以旁分泌方式起作用以促进血管生成和肿瘤生长。因此，抑制IL 6可具有治疗以致癌Ras突变为特征的癌症的治疗效用。
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.