Fructose 2,6-Bisphosphate in Cancer Cell Metabolism.
Fructose 2,6-Bisphosphate in Cancer Cell Metabolism.
复制标题
DOI：
10.3389/fonc.2018.00331
复制
发表时间：
2018
影响因子：
4.7
通讯作者：
Martinez-Outschoorn UE
中科院分区：
文献类型：
--
作者：
Bartrons R;Simon-Molas H;Rodríguez-García A;Castaño E;Navarro-Sabaté À;Manzano A;Martinez-Outschoorn UE
长期以来，癌细胞新陈代谢领域的先驱，如奥托·沃伯格，一直专注于肿瘤细胞即使在充足的氧气供应下仍保持高糖酵解率的观点，即所谓的有氧糖酵解或沃伯格效应。最近的研究报告了一种更复杂的情况，肿瘤生态系统在癌症进展中扮演着更关键的角色。癌细胞在适应肿瘤微环境的变化、制定生存和增殖策略方面表现出非凡的可塑性。癌细胞的增殖需要高速率的能量和代谢底物来合成生物分子。癌细胞和肿瘤微环境中存在的其他细胞的代谢重新编程满足了这些要求，这对肿瘤的生存和扩散是必不可少的。代谢重编程涉及癌基因、肿瘤抑制因子、生长因子和肿瘤微环境中的局部因素之间的复杂相互作用。这些因子可以诱导基质细胞和癌细胞中不同于正常细胞表达的糖酵解同工酶和蛋白质的过度表达和活性增加。Fructose-6-phosphate/fructose-1，6-bisphosphate循环由6-磷酸果糖-1-激酶/果糖1，6-二磷酸酶同工酶催化，在控制糖酵解速率中起着关键作用。PFK1/FBpase1的活性受果糖-2，6-二磷酸的变构调节，果糖-2，6-二磷酸是6-磷酸果糖-2-激酶/果糖2，6-二磷酸酶(6-磷酸果糖-2-激酶/果糖2，6-二磷酸酶)和TP53诱导的糖酵解和凋亡调节因子(TIGAR)的双重酶家族活性的产物，在许多肿瘤类型中表达增加。本文综述了这些同工酶在代谢调节中的作用，以及调节它们在肿瘤生态系统中的表达和活性的调节因子。以这些同工酶为靶点，直接或通过抑制其激活因子，可能是治疗癌症的一种有前途的方法。
For a long time, pioneers in the field of cancer cell metabolism, such as Otto Warburg, have focused on the idea that tumor cells maintain high glycolytic rates even with adequate oxygen supply, in what is known as aerobic glycolysis or the Warburg effect. Recent studies have reported a more complex situation, where the tumor ecosystem plays a more critical role in cancer progression. Cancer cells display extraordinary plasticity in adapting to changes in their tumor microenvironment, developing strategies to survive and proliferate. The proliferation of cancer cells needs a high rate of energy and metabolic substrates for biosynthesis of biomolecules. These requirements are met by the metabolic reprogramming of cancer cells and others present in the tumor microenvironment, which is essential for tumor survival and spread. Metabolic reprogramming involves a complex interplay between oncogenes, tumor suppressors, growth factors and local factors in the tumor microenvironment. These factors can induce overexpression and increased activity of glycolytic isoenzymes and proteins in stromal and cancer cells which are different from those expressed in normal cells. The fructose-6-phosphate/fructose-1,6-bisphosphate cycle, catalyzed by 6-phosphofructo-1-kinase/fructose 1,6-bisphosphatase (PFK1/FBPase1) isoenzymes, plays a key role in controlling glycolytic rates. PFK1/FBpase1 activities are allosterically regulated by fructose-2,6-bisphosphate, the product of the enzymatic activity of the dual kinase/phosphatase family of enzymes: 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFKFB1-4) and TP53-induced glycolysis and apoptosis regulator (TIGAR), which show increased expression in a significant number of tumor types. In this review, the function of these isoenzymes in the regulation of metabolism, as well as the regulatory factors modulating their expression and activity in the tumor ecosystem are discussed. Targeting these isoenzymes, either directly or by inhibiting their activating factors, could be a promising approach for treating cancers.
登录
查看更多内容
影响因子：
11.4
作者：
Bensaad, Karim;Cheung, Eric C.;Vousden, Karen H.
通讯作者：
Vousden, Karen H.
影响因子：
4.8
作者：
Chan, Olivia;Burke, J. Daniel;Fish, Eleanor N.
通讯作者：
Fish, Eleanor N.
DOI：
10.1016/j.bbrc.2012.12.109
发表时间：
2013-02-01
影响因子：
3.1
作者：
Cosin-Roger, Jesus;Vernia, Santiago;Casado, Marta
通讯作者：
Casado, Marta
影响因子：
50.3
作者：
Cantelmo AR;Conradi LC;Brajic A;Goveia J;Kalucka J;Pircher A;Chaturvedi P;Hol J;Thienpont B;Teuwen LA;Schoors S;Boeckx B;Vriens J;Kuchnio A;Veys K;Cruys B;Finotto L;Treps L;Stav-Noraas TE;Bifari F;Stapor P;Decimo I;Kampen K;De Bock K;Haraldsen G;Schoonjans L;Rabelink T;Eelen G;Ghesquière B;Rehman J;Lambrechts D;Malik AB;Dewerchin M;Carmeliet P
通讯作者：
Carmeliet P
影响因子：
4
作者：
Balkwill, Frances R.;Capasso, Melania;Hagemann, Thorsten
通讯作者：
Hagemann, Thorsten