1. Autocrine IL-6 Signaling: A Key Event in Tumorigenesis?
Sergei Grivennikov, Michael Karin 
Cancer Cell 
Volume 13, Issue 1, Pages 7-9 (January 2008)
DOI: /j.ccr
Copyright © 2008 Elsevier Inc. Terms and Conditions

2. Figure 1 The Role of IL-6 Signaling in Cancer Cells
(A) In lung adenocarcinoma cells, somatic mutations in EGFR activate IL-6 transcription by an as yet unidentified mechanism. IL-6 is secreted by cancer cells and activates STAT3, which sustains tumor growth and proliferation. Contribution of infiltrating immune/inflammatory cells in vivo is also possible, and they can provide both IL-6 and soluble IL-6R (sIL-6R).
(B) IL-6-dependent STAT3 activation results in numerous downstream events required for tumor growth. Sansone et al. found an important role of the IL-6/Notch/Jagged pathway, which activates expression of the hypoxia resistance gene CA-IX. It remains to be determined whether Notch induction by IL-6 requires STAT3 or the SHP2/Erk pathway. Other IL-6/STAT3-dependent pathways include production of IL-6, activation of genes required for cell survival and proliferation (c-Myc, Cyclin D, Bcl2), and inactivation of tumor suppressor (FoxP3).
Cancer Cell  , 7-9DOI: ( /j.ccr )
Copyright © 2008 Elsevier Inc. Terms and Conditions