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肝再生磷酸酶是癌细胞代谢的关键调节剂——丝氨酸/甘氨酸代谢的作用。

Phosphatases of regenerating liver are key regulators of metabolism in cancer cells - role of Serine/Glycine metabolism.

机构信息

Center for Myeloma Research, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU).

Laboratory Clinic.

出版信息

Curr Opin Clin Nutr Metab Care. 2022 Jan 1;25(1):50-55. doi: 10.1097/MCO.0000000000000797.

Abstract

PURPOSE OF REVIEW

Phosphatases of regenerating liver (PRL) are dual-specificity phosphatases and comprise three members, PRL-1, -2 and -3. Despite the importance of PRLs as oncoproteins, there is no consensus function for this family of phosphatases. In the current review paper, we summarize recent findings on the role of PRLs in metabolic regulation.

RECENT FINDINGS

Reprogramming of cellular metabolism is a cancer hallmark. Glucose is the major source of energy in cells. Glucose metabolism occurs through the glycolysis and can continue through the pathways such as serine synthesis pathway or the tricarboxylic acid cycle (TCA). Magnesium (Mg2+), the second most abundant cation in cells, plays an essential role in energy production by acting as a cofactor for most enzymes involved in glycolysis and in TCA. Recent findings have shown that the PRL family has a role in metabolic reprogramming mediated by (1) Mg2+ homeostasis, (2) shifting the energy source preference to glucose consumption and fueling serine/glycine pathway and (3) regulating PI3 kinase/Mammalian target of rapamycin complex. Both the phosphatase and nonphosphatase activity of PRLs appear to be important for its oncogenic role.

SUMMARY

The PRL family contributes to the metabolic plasticity of cancer cells and, thereby, allows cancer cells to meet the high metabolic demands required for cell proliferation.

摘要

目的综述

肝再生磷酸酶(PRL)是双特异性磷酸酶,由三个成员 PRL-1、-2 和 -3 组成。尽管 PRL 作为癌蛋白非常重要,但这个磷酸酶家族的功能尚未达成共识。在本期综述中,我们总结了 PRL 在代谢调节中的作用的最新发现。

最新发现

细胞代谢重编程是癌症的一个标志。葡萄糖是细胞的主要能量来源。葡萄糖代谢通过糖酵解进行,并且可以通过丝氨酸合成途径或三羧酸循环(TCA)等途径继续进行。镁(Mg2+),细胞中第二丰富的阳离子,作为大多数参与糖酵解和 TCA 的酶的辅助因子,在能量产生中发挥着重要作用。最近的发现表明,PRL 家族在代谢重编程中具有作用,这种重编程是由(1)Mg2+ 稳态、(2)将能量来源偏好转移到葡萄糖消耗和为丝氨酸/甘氨酸途径供能、(3)调节 PI3 激酶/雷帕霉素哺乳动物靶蛋白复合物介导的。PRL 的磷酸酶和非磷酸酶活性似乎对其致癌作用都很重要。

总结

PRL 家族有助于癌细胞的代谢可塑性,从而使癌细胞能够满足细胞增殖所需的高代谢需求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b478/8694249/85f05e74c826/cocnm-25-50-g001.jpg

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