Liu Yulin, Xiang Fan, Huang Yongming, Shi Liang, Hu Chaojie, Yang Yiming, Wang Di, He Nan, Tao Kaixiong, Wu Ke, Wang Guobin
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Oncotarget. 2017 Apr 11;8(15):25372-25383. doi: 10.18632/oncotarget.15913.
Interleukin-22 has been explored extensively in human cancer, but its functions and underlying mechanisms are incompletely understood. Here, we show that aberrant interleukin-22 expression facilitates aerobic glycolysis in colon cancer cells. Elevated interleukin-22 mRNA expression was observed and positively correlated with hexokinase-2 in colon cancer tissues. In vitro, interleukin-22 enhanced glucose consumption and lactate production via targeting hexokinase-2 in colon cancer cells. Moreover, the transcriptional factor c-Myc and signal transducer and activator of transcription 3 were involved in interleukin-22-induced up-regulation of hexokinase-2. We further demonstrated that hexokinase-2 partly accounted for interleukin-22-mediated cellular proliferation in DLD-1 cells. In vivo, our data demonstrated that interleukin-22 significantly promoted tumor growth along with elevated expression of c-Myc and hexokinase-2 in mice. In summary, our findings provide a new perspective on the pro-inflammatory cytokine interleukin-22 in promoting aerobic glycolysis associated with tumor progression in human colon cancer cells.
白细胞介素-22已在人类癌症中得到广泛研究，但其功能和潜在机制尚未完全明确。在此，我们表明白细胞介素-22的异常表达促进结肠癌细胞的有氧糖酵解。在结肠癌组织中观察到白细胞介素-22 mRNA表达升高，且与己糖激酶-2呈正相关。在体外，白细胞介素-22通过靶向结肠癌细胞中的己糖激酶-2增强葡萄糖消耗和乳酸生成。此外，转录因子c-Myc和信号转导及转录激活因子3参与白细胞介素-22诱导的己糖激酶-2上调。我们进一步证明己糖激酶-2部分解释了白细胞介素-22介导的DLD-1细胞增殖。在体内，我们的数据表明白细胞介素-22显著促进小鼠肿瘤生长，同时c-Myc和己糖激酶-2表达升高。总之，我们的研究结果为促炎细胞因子白细胞介素-22在促进人类结肠癌细胞中与肿瘤进展相关的有氧糖酵解方面提供了新的视角。
