The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing, China.
Cancer Res. 2018 Aug 15;78(16):4549-4562. doi: 10.1158/0008-5472.CAN-17-4047. Epub 2018 Jun 19.
Tumor cells alter their metabolism to meet their demand for macromolecules and support a high rate of proliferation as well as cope with oxidative stress. The transcription factor yin yang 1 (YY1) is upregulated in various types of tumors and is crucial for tumor cell proliferation and metastasis. However, its role in tumor cell metabolic reprogramming is poorly understood. Here, we show that YY1 alters tumor cell metabolism by activating glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway. By stimulating the pentose phosphate pathway, YY1 enhanced production of nucleotides and DNA synthesis, decreased intracellular reactive oxygen species levels, and promoted antioxidant defense by supplying increased reducing power in the form of NADPH. Importantly, YY1-mediated regulation of the pentose phosphate pathway in tumor cells occurred not through p53, but rather through direct activation of G6PD transcription by YY1. Regulation of pentose phosphate pathway activity through G6PD was strongly related to YY1-induced proliferation of tumor cells and tumorigenesis. Together, our results describe a novel role for YY1 in regulating G6PD in a p53-independent manner, which links its function in tumorigenesis to metabolic reprogramming in tumor cells. This study reveals a novel role for YY1 in regulating G6PD and activating the pentose phosphate pathway, linking its function in tumorigenesis to metabolic reprogramming. .
肿瘤细胞改变其代谢以满足大分子的需求，并支持高增殖率以及应对氧化应激。转录因子阴阳 1 (YY1) 在各种类型的肿瘤中上调，对肿瘤细胞增殖和转移至关重要。然而，其在肿瘤细胞代谢重编程中的作用知之甚少。在这里，我们表明 YY1 通过激活葡萄糖-6-磷酸脱氢酶 (G6PD) 来改变肿瘤细胞的代谢，G6PD 是戊糖磷酸途径中的限速酶。通过刺激戊糖磷酸途径，YY1 增强核苷酸的产生和 DNA 合成，降低细胞内活性氧水平，并通过提供增加的还原能力 NADPH 形式促进抗氧化防御。重要的是，YY1 介导的肿瘤细胞戊糖磷酸途径的调节不是通过 p53，而是通过 YY1 直接激活 G6PD 转录。通过 G6PD 调节戊糖磷酸途径活性与 YY1 诱导的肿瘤细胞增殖和肿瘤发生密切相关。总之，我们的研究结果描述了 YY1 以一种不依赖 p53 的方式调节 G6PD 的新作用，它将其在肿瘤发生中的功能与肿瘤细胞中的代谢重编程联系起来。这项研究揭示了 YY1 在调节 G6PD 和激活戊糖磷酸途径中的新作用，将其在肿瘤发生中的功能与肿瘤细胞中的代谢重编程联系起来。
