负反馈循环是瓦尔堡效应的基础。
A negative feedback loop underlies the Warburg effect.
发表日期:2024 May 24
作者:
Alok Jaiswal, Raghvendra Singh
来源:
npj Systems Biology and Applications
摘要:
癌细胞利用有氧糖酵解或瓦伯格效应进行增殖,同时产生乳酸。尽管乳酸的产生对癌症进展具有广泛的影响,但尚不清楚这种作用如何增加细胞增殖并与氧化磷酸化相关。在这里,我们阐明了负反馈循环 (NFL) 是造成瓦尔堡效应的原因。此外,我们表明有氧糖酵解可以作为氧化磷酸化的放大器。另一方面,静止是癌症干细胞的一个重要特性。基于NFL,我们发现有氧糖酵解和氧化磷酸化两者发挥协同作用,是实现细胞静止所必需的。此外,我们的结果表明,缺氧环境中的细胞高度增殖,但通过缺氧的严重程度增加其 NADH/NAD 比率,从而接近达到静止状态。这项研究的结果有助于更好地理解新陈代谢、细胞周期、致癌作用和干性之间的联系。© 2024。作者。
Aerobic glycolysis, or the Warburg effect, is used by cancer cells for proliferation while producing lactate. Although lactate production has wide implications for cancer progression, it is not known how this effect increases cell proliferation and relates to oxidative phosphorylation. Here, we elucidate that a negative feedback loop (NFL) is responsible for the Warburg effect. Further, we show that aerobic glycolysis works as an amplifier of oxidative phosphorylation. On the other hand, quiescence is an important property of cancer stem cells. Based on the NFL, we show that both aerobic glycolysis and oxidative phosphorylation, playing a synergistic role, are required to achieve cell quiescence. Further, our results suggest that the cells in their hypoxic niche are highly proliferative yet close to attaining quiescence by increasing their NADH/NAD+ ratio through the severity of hypoxia. The findings of this study can help in a better understanding of the link among metabolism, cell cycle, carcinogenesis, and stemness.© 2024. The Author(s).