Pyruvate Kinase M1/2 Proteoformics for Accurate Insights into Energy Metabolism Abnormity to Promote the Overall Management of Ovarian Cancer Towards Predictive, Preventive, and Personalized Medicine Approaches.

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Metabolites Pub Date : 2025-03-16 DOI:10.3390/metabo15030203

Yan Wang, Nuo Xu, Marie Louise Ndzie Noah, Liang Chen, Xianquan Zhan

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引用次数: 0

Abstract

Ovarian cancer (OC) is a global health problem that frequently presents at advanced stages, is predisposed to recurrence, readily develops resistance to platinum-based drugs, and has a low survival rate. Predictive, preventive, and personalized medicine (PPPM/3PM) offers an integrated solution with the use of genetic, proteomic, and metabolic biomarkers to identify high-risk individuals for early detection. Metabolic reprogramming is one of the key strategies employed by tumor cells to adapt to the microenvironment and support unlimited proliferation. Pyruvate kinases M1 and M2 (PKM1/2) are encoded by the PKM gene, a pivotal enzyme in the last step of the glycolytic pathway, which is at the crossroads of aerobic oxidation and the Warburg effect to serve as a potential regulator of glucose metabolism and influence cellular energy production and metabolic reprogramming. Commonly, the ratio of PKM1-to-PKM2 is changed in tumors compared to normal controls, and PKM2 is highly expressed in OC to induce a high glycolysis rate and participate in the malignant invasion and metastatic characteristics of cancer cells with epithelial/mesenchymal transition (EMT). PKM2 inhibitors suppress the migration and growth of OC cells by interfering with the Warburg effect. Proteoforms are the final structural and functional forms of a gene/protein, and the canonical protein PKM contains all proteoforms encoded by the same PKM gene. The complexity of PKM can be elucidated by proteoformics. The OC-specific PKM proteoform might represent a specific target for therapeutic interventions against OC. In the framework of PPPM/3PM, the OC-specific PKM proteoform might be the early warning and prognosis biomarker. It is important to clarify the molecular mechanisms of PKM proteoforms in cancer metabolism. This review analyzes the expression, function, and molecular mechanisms of PKM proteoforms in OC, which help identify specific biomarkers for OC.

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丙酮酸激酶M1/2蛋白组学对能量代谢异常的准确洞察，促进卵巢癌的整体管理向预测、预防和个性化医学方向发展。

卵巢癌（OC）是一个全球性的健康问题，经常出现在晚期，易于复发，容易对含铂药物产生耐药性，生存率低。预测性、预防性和个性化医学（PPPM/3PM）提供了一种集成的解决方案，使用遗传、蛋白质组学和代谢生物标志物来识别高风险个体，以便早期发现。代谢重编程是肿瘤细胞适应微环境和支持无限增殖的关键策略之一。丙酮酸激酶M1和M2 （PKM1/2）由PKM基因编码，PKM基因是糖酵解途径最后一步的关键酶，处于有氧氧化和Warburg效应的十字路口，是葡萄糖代谢的潜在调节因子，影响细胞能量产生和代谢重编程。通常，与正常对照相比，肿瘤中pkm1与PKM2的比例发生变化，PKM2在OC中高表达，诱导高糖酵解率，参与上皮/间充质转化（epithelial/mesenchymal transition， EMT）癌细胞的恶性侵袭和转移特征。PKM2抑制剂通过干扰Warburg效应抑制OC细胞的迁移和生长。蛋白质形态是基因/蛋白质的最终结构和功能形态，典型蛋白PKM包含由同一PKM基因编码的所有蛋白质形态。PKM的复杂性可以通过蛋白质组学来阐明。OC特异性PKM蛋白形式可能是针对OC的治疗干预的特定靶点。在PPPM/3PM的框架下，oc特异性PKM蛋白形态可能是早期预警和预后的生物标志物。阐明PKM蛋白形态在肿瘤代谢中的分子机制具有重要意义。本文分析了PKM蛋白形式在OC中的表达、功能和分子机制，有助于识别OC的特异性生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Metabolites Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

5.70

自引率

7.30%

发文量

1070

审稿时长

17.17 days

期刊介绍： Metabolites (ISSN 2218-1989) is an international, peer-reviewed open access journal of metabolism and metabolomics. Metabolites publishes original research articles and review articles in all molecular aspects of metabolism relevant to the fields of metabolomics, metabolic biochemistry, computational and systems biology, biotechnology and medicine, with a particular focus on the biological roles of metabolites and small molecule biomarkers. Metabolites encourages scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on article length. Sufficient experimental details must be provided to enable the results to be accurately reproduced. Electronic material representing additional figures, materials and methods explanation, or supporting results and evidence can be submitted with the main manuscript as supplementary material.