IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR

A. Rojas, G. Liu, I. Coleman, P. S. Nelson, M. Zhang, R. Dash, P. B. Fisher, S. R. Plymate, J. D. Wu

Research output: Contribution to journalArticlepeer-review

119 Scopus citations


As an established mediator of inflammation, interleukin-6 (IL-6) is implicated to facilitate prostate cancer progression to androgen independence through transactivation of the androgen receptor. However, whether IL-6 has a causative role in de novo prostate tumorigenesis was never investigated. We now provide the first evidence that IL-6 can induce tumorigenic conversion and further progression to an invasive phenotype of non-tumorigenic benign prostate epithelial cells. Moreover, we find that paracrine IL-6 stimulates the autocrine IL-6 loop and autocrine activation of insulin-like type I growth factor receptor (IGF-IR) to confer the tumorigenic property and also that activation of signal transducer and activator of transcription 3 (STAT3) is critical in these processes. Inhibition of STAT3 activation or IGF-IR signaling suppresses IL-6-mediated malignant conversion and the associated invasive phenotype. Inhibition of STAT3 activation suppresses IL-6-induced upregulation of IGF-IR and its ligands, namely IGF-I and IGF-II. These findings indicate that IL-6 signaling cooperates with IGF-IR signaling in the prostate microenvironment to promote prostate tumorigenesis and progression to aggressiveness. Our findings suggest that STAT3 and IGF-IR may represent potential effective targets for prevention or treatment of prostate cancer.

Original languageEnglish (US)
Pages (from-to)2345-2355
Number of pages11
Issue number20
StatePublished - May 19 2011


  • EMT
  • IGF-IR
  • IL-6
  • STAT3
  • prostate
  • tumorigenesis

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Cancer Research


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