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Cancers 2014, 6(2), 741-755; doi:10.3390/cancers6020741
Review

HiJAK’d Signaling; the STAT3 Paradox in Senescence and Cancer Progression

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 and *
Received: 8 February 2014; in revised form: 8 March 2014 / Accepted: 11 March 2014 / Published: 26 March 2014
(This article belongs to the Special Issue Cytokines in Cancer)
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Abstract: Clinical and epidemiological data have associated chronic inflammation with cancer progression. Most tumors show evidence of infiltrating immune and inflammatory cells, and chronic inflammatory disorders are known to increase the overall risk of cancer development. While immune cells are often observed in early hyperplastic lesions in vivo, there remains debate over whether these immune cells and the cytokines they produce in the developing hyperplastic microenvironment act to inhibit or facilitate tumor development. The interleukin-6 (IL-6) family of cytokines, which includes IL-6 and oncostatin M (OSM), among others (LIF, CT-1, CNTF, and CLC), are secreted by immune cells, stromal cells, and epithelial cells, and regulate diverse biological processes. Each of the IL-6 family cytokines signals through a distinct receptor complex, yet each receptor complex uses a shared gp130 subunit, which is critical for signal transduction following cytokine binding. Activation of gp130 results in the activation of Signal Transducer and Activator of Transcription 3 (STAT3), and the Mitogen-Activated Protein Kinase (MAPK) and Phosphatidylinositol 3-Kinase (PI3K) signaling cascades. Tumor suppressive signaling can often be observed in normal cells following prolonged STAT3 activation. However, there is mounting evidence that the IL-6 family cytokines can contribute to later stages of tumor progression in many ways. Here we will review how the microenvironmental IL-6 family cytokine OSM influences each stage of the transformation process. We discuss the intrinsic adaptations a developing cancer cell must make in order to tolerate and circumvent OSM-mediated growth suppression, as well as the OSM effectors that are hijacked during tumor expansion and metastasis. We propose that combining current therapies with new ones that suppress the signals generated from the tumor microenvironment will significantly impact an oncologist’s ability to treat cancer.
Keywords: oncostatin M; gp130; STAT3; cytokine; senescence; transformation; inflammation oncostatin M; gp130; STAT3; cytokine; senescence; transformation; inflammation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Junk, D.J.; Bryson, B.L.; Jackson, M.W. HiJAK’d Signaling; the STAT3 Paradox in Senescence and Cancer Progression. Cancers 2014, 6, 741-755.

AMA Style

Junk DJ, Bryson BL, Jackson MW. HiJAK’d Signaling; the STAT3 Paradox in Senescence and Cancer Progression. Cancers. 2014; 6(2):741-755.

Chicago/Turabian Style

Junk, Damian J.; Bryson, Benjamin L.; Jackson, Mark W. 2014. "HiJAK’d Signaling; the STAT3 Paradox in Senescence and Cancer Progression." Cancers 6, no. 2: 741-755.



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