美国宾夕法尼亚大学Xiaolu Yang研究组在研究中取得进展。他们的研究认为细胞抗氧化能力上调和核苷酸前体可用性增加足以导致致癌性转化。这一研究成果在线发表在2020年11月6日的《细胞-代谢》上。

研究人员发现在体外过量表达的葡萄糖-6-磷酸脱氢酶（G6PD）为小鼠和人类永生化细胞提供了锚定非依赖性生长条件和动物体内的致瘤性。从机制上讲，G6PD通过激活NAD⁺激酶介导的NADP⁺生物合成来增加NADPH库，并将NADP⁺转化为NADPH，从而增强抗氧化防御能力。G6PD还通过产生核糖和NADPH来增加核苷酸前体水平，从而促进细胞增殖。

补充抗氧化剂或核苷足以将永生化的小鼠和人细胞转化为致瘤细胞，并且当最小化它们重叠代谢的影响时，需要同时补充两者。这些结果表明正常细胞具有有限的氧化还原平衡和核苷酸合成能力，克服这一局限可能代表了致癌转化的关键步骤。

研究人员表示，发生在各种正常组织的癌症代表了一组常见的基本过程。但是，人们对这些过程尚未完全理解。

附：英文原文

Title: Upregulation of Antioxidant Capacity and Nucleotide Precursor Availability Suffices for Oncogenic Transformation

Author: Yang Zhang, Yi Xu, Wenyun Lu, Jonathan M. Ghergurovich, Lili Guo, Ian A. Blair, Joshua D. Rabinowitz, Xiaolu Yang

Issue&Volume: 2020-11-06

Abstract: The emergence of cancer from diverse normal tissues has been rationalized to representa common set of fundamental processes. However, these processes are not fully defined.Here, we show that forced expression of glucose-6-phosphate dehydrogenase (G6PD) affordsimmortalized mouse and human cells anchorage-independent growth in vitro and tumorigenicity in animals. Mechanistically, G6PD augments the NADPH pool by stimulatingNAD+ kinase-mediated NADP+ biosynthesis in addition to converting NADP+ to NADPH, bolstering antioxidant defense. G6PD also increases nucleotide precursorlevels through the production of ribose and NADPH, promoting cell proliferation. Supplementationof antioxidants or nucleosides suffices to convert immortalized mouse and human cellsinto a tumorigenic state, and supplementation of both is required when their overlappingmetabolic consequences are minimized. These results suggest that normal cells havea limited capacity for redox balance and nucleotide synthesis, and overcoming thislimit might represent a key aspect of oncogenic transformation.

DOI: 10.1016/j.cmet.2020.10.002

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30535-0