National Institute of Cancer Research, National Health Research Institutes, No. 367, Shengli Road, Tainan, 704, Taiwan.
Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 802, Taiwan.
Mol Cancer. 2018 Feb 19;17(1):35. doi: 10.1186/s12943-018-0791-3.
Originally identified as a metabolic enzyme that catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP in the glycolytic pathway, pyruvate kinase M2-type (PKM2) has been shown to exhibit novel biological activities in the nucleus and outside the cells. Although cell-based studies reveal new non-canonical functions of PKM2 in gene transcription, epigenetic modulation and cell cycle progression, the importance of these non-canonical functions in PKM2-mediated tumorigenesis is still under debate because studies in genetically modified mice do not consistently echo the findings observed in cultured cancer cells. In addition to regulation of gene expression, the existence of PKM2 in exosomes opens a new venue to study the potential role of this glycolytic enzyme in cell-cell communication and extracellular signal initiation. In this review, we briefly summarize current understanding of PKM2 in metabolic switch and gene regulation. We will then emphasize recent progress of PKM2 in extracellular signaling and tumor microenvironment reprogramming. Finally, the discrepancy of some PKM2's functions in vitro and in vivo, and the application of PKM2 in cancer detection and treatment will be discussed.
最初被鉴定为一种代谢酶，可在糖酵解途径中催化从磷酸烯醇丙酮酸（PEP）向 ADP 的磷酸基团转移，丙酮酸激酶 M2 型（PKM2）已被证明在核内和细胞外具有新的生物学活性。尽管基于细胞的研究揭示了 PKM2 在基因转录、表观遗传调控和细胞周期进展中的新的非典型功能，但这些非典型功能在 PKM2 介导的肿瘤发生中的重要性仍存在争议，因为在基因修饰小鼠中的研究并不一致地反映出在培养的癌细胞中观察到的结果。除了对基因表达的调节外，PKM2 存在于外泌体中为研究这种糖酵解酶在细胞间通讯和细胞外信号起始中的潜在作用开辟了新的途径。在这篇综述中，我们简要总结了目前对 PKM2 在代谢转换和基因调控中的理解。然后，我们将强调 PKM2 在细胞外信号转导和肿瘤微环境重编程中的最新进展。最后，将讨论一些 PKM2 的功能在体外和体内的差异，以及 PKM2 在癌症检测和治疗中的应用。
