PDF(Pubmed)
Abstract：
The tumor cells reprogram their metabolism to cover their high bioenergetic demands for maintaining uncontrolled growth. This response can be mediated by cytokines such as IL-2, which binds to its receptor and activates the JAK/STAT pathway. Some reports show a correlation between the JAK/STAT pathway and cellular metabolism, since the constitutive activation of STAT proteins promotes glycolysis through the transcriptional activation of genes related to energetic metabolism. However, the role of STAT proteins in the metabolic switch induced by cytokines in cervical cancer remains poorly understood. In this study, we analyzed the effect of IL-2 on the metabolic switch and the role of STAT5 in this response. Our results show that IL-2 induces cervical cancer cell proliferation and the tyrosine phosphorylation of STAT5. Also, it induces an increase in lactate secretion and the ratio of NAD+/NADH, which suggest a metabolic reprogramming of their metabolism. When STAT5 was silenced, the lactate secretion and the NAD+/NADH ratio decreased. Also, the expression of HIF1α and GLUT1 decreased. These results indicate that STAT5 regulates IL-2-induced cell proliferation and the metabolic shift to aerobic glycolysis by regulating genes related to energy metabolism. Our results suggest that STAT proteins modulate the metabolic switch in cervical cancer cells to attend to their high demand of energy required for cell growth and proliferation.
摘要：
肿瘤细胞重新编程其代谢以覆盖其维持不受控制的生长的高生物能需求。这种反应可以由细胞因子如IL-2介导,其结合其受体并激活JAK/STAT途径。一些报道显示JAK/STAT通路与细胞代谢之间存在相关性,因为STAT蛋白的组成型激活通过与能量代谢相关的基因的转录激活促进糖酵解。然而,STAT蛋白在宫颈癌细胞因子诱导的代谢开关中的作用尚不清楚.在这项研究中,我们分析了IL-2对代谢开关的影响以及STAT5在该反应中的作用.我们的结果表明IL-2诱导宫颈癌细胞增殖和STAT5的酪氨酸磷酸化。此外，它诱导乳酸分泌和NAD+/NADH的比例增加，这表明它们的新陈代谢重新编程。当STAT5沉默时，乳酸分泌和NAD+/NADH比值降低。此外，HIF1α和GLUT1表达降低。这些结果表明STAT5通过调节与能量代谢相关的基因来调节IL-2诱导的细胞增殖和向有氧糖酵解的代谢转变。我们的结果表明，STAT蛋白调节子宫颈癌细胞中的代谢开关，以满足其对细胞生长和增殖所需能量的高需求。
