Ando Masaru, Uehara Ikuno, Kogure Kayo, Asano Yumi, Nakajima Wataru, Abe Yoshinori, Kawauchi Keiko, Tanaka Nobuyuki
Department of Molecular Oncology, Graduate School of Medicine, Nippon Medical School.
J Nippon Med Sch. 2010 Apr;77(2):97-105. doi: 10.1272/jnms.77.97.
Enhanced glycolysis is important for oncogenesis and for the survival and proliferation of cancer cells in the tumor microenvironment. Recent studies have also shown that proinflammatory cytokine signaling, such as that mediated by nuclear factor kappaB and signal transducer and activator of transcription 3 (STAT3), is important for the generation of inflammation-associated tumors. However, the link between inflammation and enhanced glycolysis has not been identified. In the present study, we found that the proinflammatory cytokine interleukin (IL)-6 enhanced glycolysis in mouse embryonic fibroblasts and human cell lines. Moreover, STAT3 activated by IL-6 enhanced the expression of the glycolytic enzymes hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3). Ectopic expression of PFKFB3 enhanced glycolysis, suggesting that the IL-6-STAT3 pathway enhances glycolysis through the induction of these enzymes. Our findings may provide a novel mechanism for inflammation-associated oncogenesis.
增强的糖酵解对于肿瘤发生以及肿瘤微环境中癌细胞的存活和增殖至关重要。最近的研究还表明，促炎细胞因子信号传导，如由核因子κB和信号转导及转录激活因子3（STAT3）介导的信号传导，对于炎症相关肿瘤的产生很重要。然而，炎症与增强的糖酵解之间的联系尚未明确。在本研究中，我们发现促炎细胞因子白细胞介素（IL）-6增强了小鼠胚胎成纤维细胞和人类细胞系中的糖酵解。此外，由IL-6激活的STAT3增强了糖酵解酶己糖激酶2和6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶-3（PFKFB3）的表达。PFKFB3的异位表达增强了糖酵解，这表明IL-6-STAT3途径通过诱导这些酶来增强糖酵解。我们的发现可能为炎症相关的肿瘤发生提供一种新机制。
