Pyruvate kinase M2 fuels multiple aspects of cancer cells: from cellular metabolism, transcriptional regulation to extracellular signaling.
Pyruvate kinase M2 fuels multiple aspects of cancer cells: from cellular metabolism, transcriptional regulation to extracellular signaling.
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DOI：
10.1186/s12943-018-0791-3
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发表时间：
2018-02-19
期刊：
影响因子：
37.3
通讯作者：
Hung WC
中科院分区：
文献类型：
--
作者：
Hsu MC;Hung WC
丙酮酸激酶M2型（PKM2）最初被鉴定为在糖酵解途径中催化磷酸基团从磷酸烯醇式丙酮酸（PEP）转移到ADP的代谢酶，已被证明在细胞核和细胞外表现出新的生物活性。尽管基于细胞的研究揭示了PKM2在基因转录、表观遗传调节和细胞周期进展中的新的非经典功能，但这些非经典功能在PKM2介导的肿瘤发生中的重要性仍在争论中，因为在转基因小鼠中的研究并不一致地反映在培养的癌细胞中观察到的发现。除了调控基因表达外，PKM2在外来体中的存在为研究这种糖酵解酶在细胞间通讯和细胞外信号启动中的潜在作用开辟了新的途径。本文就PKM2在代谢开关和基因调控中的研究进展作一综述。我们将重点介绍PKM2在细胞外信号传导和肿瘤微环境重编程方面的最新进展。最后，对PKM2在体内外功能的差异以及PKM2在肿瘤检测和治疗中的应用进行了讨论。
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.
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与丙酮酸激酶 M2 的相互作用通过蛋白酶体降解破坏 Tristetraprolin 的稳定性并调节乳腺癌中的细胞增殖。
影响因子：
4.6
作者：
Huang L;Yu Z;Zhang Z;Ma W;Song S;Huang G
通讯作者：
Huang G
影响因子：
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作者：
Hu W;Lu SX;Li M;Zhang C;Liu LL;Fu J;Jin JT;Luo RZ;Zhang CZ;Yun JP
通讯作者：
Yun JP
影响因子：
4.7
作者：
Hacker, HJ;Steinberg, P;Bannasch, P
通讯作者：
Bannasch, P
丙酮酸激酶M2激活剂促进四聚体形成并抑制肿瘤发生。
影响因子：
14.8
作者：
Anastasiou, Dimitrios;Yu, Yimin;Israelsen, William J.;Jiang, Jian-Kang;Boxer, Matthew B.;Hong, Bum Soo;Tempel, Wolfram;Dimov, Svetoslav;Shen, Min;Jha, Abhishek;Yang, Hua;Mattaini, Katherine R.;Metallo, Christian M.;Fiske, Brian P.;Courtney, Kevin D.;Malstrom, Scott;Khan, Tahsin M.;Kung, Charles;Skoumbourdis, Amanda P.;Veith, Henrike;Southall, Noel;Walsh, Martin J.;Brimacombe, Kyle R.;Leister, William;Lunt, Sophia Y.;Johnson, Zachary R.;Yen, Katharine E.;Kunii, Kaiko;Davidson, Shawn M.;Christofk, Heather R.;Austin, Christopher P.;Inglese, James;Harris, Marian H.;Asara, John M.;Stephanopoulos, Gregory;Salituro, Francesco G.;Jin, Shengfang;Dang, Lenny;Auld, Douglas S.;Park, Hee-Won;Cantley, Lewis C.;Thomas, Craig J.;Heiden, Matthew G. Vander
通讯作者：
Heiden, Matthew G. Vander
影响因子：
10.3
作者：
Gordon, Gavin J.;Dong, Lingsheng;Bueno, Raphael
通讯作者：
Bueno, Raphael