Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis.
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.
Ancrile
Brooke
B
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Lim
Kian-Huat
KH
Counter
Christopher M
CM
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000209:etiology / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D012313:RNA / Q000235:genetics; D000093242:Interleukin-6 Inhibitors
D015850:Interleukin-6; D012313:RNA; D000093242:Interleukin-6 Inhibitors