National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Institute of Veterinary Physiology and Biochemistry, University of Giessen, Frankfurter Strasse 100, 35392 Giessen, Germany.
FEBS Lett. 2014 Aug 19;588(16):2685-92. doi: 10.1016/j.febslet.2014.04.011. Epub 2014 Apr 18.
Cancer cells are characterized by high glycolytic rates to support energy regeneration and anabolic metabolism, along with the expression of pyruvate kinase isoenzyme M2 (PKM2). The latter catalyzes the last step of glycolysis and reprograms the glycolytic flux to feed the special metabolic demands of proliferating cells. Besides, PKM2 has moonlight functions, such as gene transcription, favoring cancer. Accumulating evidence suggests a critical role played by the low-activity-dimeric PKM2 in tumor progression, supported by the identification of mutations which result in the down-regulation of its activity and tumorigenesis in a nude mouse model. This review discusses PKM2 regulation and the benefits it confers to cancer cells. Further, conflicting views on PKM2's role in cancer, its therapeutic relevance and future directions in the field are also discussed.
癌细胞的特征是糖酵解率高，以支持能量再生和合成代谢，同时表达丙酮酸激酶同工酶 M2（PKM2）。后者催化糖酵解的最后一步，重新编程糖酵解通量，以满足增殖细胞的特殊代谢需求。此外，PKM2 还有月光功能，如促进癌症的基因转录。越来越多的证据表明，低活性二聚体 PKM2 在肿瘤进展中起着关键作用，这一观点得到了支持，因为已经鉴定出导致其活性下调的突变，并在裸鼠模型中导致肿瘤发生。本文讨论了 PKM2 的调节及其赋予癌细胞的益处。此外，还讨论了 PKM2 在癌症中的作用、治疗相关性以及该领域的未来方向存在的矛盾观点。
