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Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors

Oncogene volume 19, pages 2548–2556 (2000)Cite this article

Abstract

Members of the IL-6 cytokine family are involved in a variety of biological responses, including the immune response, inflammation, hematopoiesis, and oncogenesis by regulating cell growth, survival, and differentiation. These cytokines use gp130 as a common receptor subunit. The binding of ligand to gp130 activates the JAK/STAT signal transduction pathway, where STAT3 plays a central role in transmitting the signals from the membrane to the nucleus. STAT3 is essential for gp130-mediated cell survival and G1 to S cell-cycle-transition signals. Both c-myc and pim have been identified as target genes of STAT3 and together can compensate for STAT3 in cell survival and cell-cycle transition. STAT3 is also required for gp130-mediated maintenance of the pluripotential state of proliferating embryonic stem cells and for the gp130-induced macrophage differentiation of M1 cells. Furthermore, STAT3 regulates cell movement, such as leukocyte, epidermal cell, and keratinocyte migration. STAT3 also appears to regulate B cell differentiation into antibody-forming plasma cells. Since the IL-6/gp130/STAT3 signaling pathway is involved in both B cell growth and differentiation into plasma cells it is likely to play a central role in the generation of plasma cell neoplasias.

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Acknowledgements

We would like to thank all members of our laboratory for their excellent contributions to our studies and valuable comments and discussions. We also thank Ms R Masuda and Ms A Kubota for their secretarial assistance. The work performed in our laboratory was supported by grants and a Grant-in-Aid for COE Research from the Ministry of Education, Science, Sports, and Culture in Japan, and grants from the Osaka Foundation for the Promotion of Clinical Immunology.

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  1. Division of Molecular Oncology C-7, Biomedical Research Center, Osaka University Graduate School of Medicine, 2-2 Yamada-oko, Suita, 565-0871, Osaka, Japan

    Toshio Hirano, Katsuhiko Ishihara & Masahiko Hibi

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Hirano, T., Ishihara, K. & Hibi, M. Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene 19, 2548–2556 (2000). https://doi.org/10.1038/sj.onc.1203551

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