DNA damage induces the IL-6/STAT3 signaling pathway, which has anti-senescence and growth-promoting functions in human tumors |
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Authors: | Yun Un Jung Park Sang Eun Jo Yong Sam Kim Jungbin Shin Deug Y |
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Institution: | Aging-Cancer Research Center and Department of Microbiology, College of Medicine, Dankook University, Anseo 29, Cheonan 330-714, Republic of Korea. |
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Abstract: | IL-6 is a multifunctional cytokine that is important for immune responses, cell survival, apoptosis, and proliferation. However, little is known about the correlation between the IL-6 signaling pathway and DNA damage in human tumors. The present study demonstrates the role of the IL-6/STAT3 signaling pathway in human tumor cells exposed to DNA damage. Tumor cells exposed to DNA damage increase the expression and secretion of IL-6 and the phosphorylation of JAK1 and STAT3. The activation of the JAK1-STAT3 signaling pathway is inhibited by knockdown of gp130 or neutralization of soluble IL-6, implying that DNA damage induces the phosphorylation of JAK1 and STAT3 by autocrine IL-6. Interestingly, inhibition of the IL-6/STAT3 signaling pathway impairs the growth of tumor cells exposed to DNA damage and results in the induction of senescence. Therefore, the present study suggests that IL-6 inhibits senescence but promotes the survival and proliferation of tumor cells exposed to DNA damage through the activation of the JAK1-STAT3 signaling pathway. |
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Keywords: | IL-6 STAT3 Senescence DNA damage Tumor |
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