title: DNA damage induces the IL-6/STAT3 signaling pathway, which has anti-senescence and growth-promoting functions in human tumors.
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.
authors.affiliation: Aging-Cancer Research Center and Department of Microbiology, College of Medicine, Dankook University, Anseo 29, Cheonan 330-714, Republic of Korea.
authors.forename: Un Jung
authors.initials: UJ
authors.lastname: Yun
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Park
authors.forename: Yong Sam
authors.initials: YS
authors.lastname: Jo
authors.forename: Jungbin
authors.initials: J
authors.lastname: Kim
authors.forename: Deug Y
authors.initials: DY
authors.lastname: Shin
mesh_terms: D001483:Base Sequence; D002455:Cell Division; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D004249:DNA Damage; D017931:DNA Primers; D020868:Gene Silencing; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human