Pyruvate Kinase Type M2: A Key Regulator Within the Tumour Metabolome and a Tool for Metabolic Profiling of Tumours
Normal proliferating cells and tumour cells in particular express the pyruvate kinase isoenzyme type M2 (M2-PK, PKM2). The quaternary structure of M2-PK determines whether the glucose carbons are degraded to pyruvate and lactate with production of energy (tetrameric form) or channelled into synthetic processes, debranching from glycolytic intermediates such as nucleic acid, amino acid and phospholipid synthesis. The tetramer:dimer ratio of M2-PK is regulated by metabolic intermediates, such as fructose 1,6-P2 and direct interaction with different oncoproteins, such as pp60v-src kinase, HPV-16 E7 and A-Raf. The metabolic function of the interaction between M2-PK and the HERC1 oncoprotein remains unknown. Thus, M2-PK is a meeting point for different oncogenes and metabolism. In tumour cells, the dimeric form of M2-PK is predominant and has therefore been termed Tumour M2-PK. Tumour M2-PK is released from tumours into the blood and from gastrointestinal tumours also into the stool of tumour patients. The quantification of Tumour M2-PK in EDTA plasma and stool is a tool for early detection of tumours and therapy control.
KeywordsPyruvate Kinase Dimeric Form Rous Sarcoma Virus Tetrameric Form Normal Proliferate Cell
This chapter is dedicated to Prof. Dr. Erich Eigenbrodt, head of the Comparative Biochemistry of Animals Department within the Veterinary Faculty of the University of Giessen, who significantly contributed to our knowledge of the role of M2-PK within the tumour metabolome and diagnosis and passed away in 2004.
- Ahmed AS, Dew T, Lawton FG, Papadopoulos AJ, Devaja O, Raju KS, Sherwood RA (2007) M2-PK as a novel marker in ovarian cancer: a prospective cohort study. Eur J Gynaec Oncol 28:83–88Google Scholar
- Eigenbrodt R, Reinacher M, Scheefers-Borchel U, Scheefers H, Friis RR (1992) Double role of pyruvate kinase type M2 in the expansion of phosphometabolite pools found in tumor cells. In: Perucho M (ed) Critical reviews in oncogenesis. CRC Press, Boca Raton, FL, pp. 91–115Google Scholar
- Eigenbrodt E, Mazurek S, Friis R (1998) Double role of pyruvate kinase type M2 in the regulation of phosphometabolite pools. In: Bannasch P, Kanduc D, Papa S, Tager JM (eds) Cell growth and oncogenesis. Birkhäuser Verlag, Basel, pp. 15–30Google Scholar
- Hardt PD, Mazurek S, Klör HU, Eigenbrodt E (2004a) Neuer Test zum Nachweis von Darmkrebs. Spiegel der Forschung 21:15–19Google Scholar
- Mazurek S (2008) Das Tumor-Metabolom – eine Quelle von Messgrößen zur frühzeitigen Diagnose von Tumoren. In: Hardt PD (ed) Tumormarker in der Gastroenterologie. Unimed Verlag, Bremen, pp 55–65Google Scholar
- Prakash O, Bardot SF, Cole JT (2007) Chicken sarcoma to human cancers: a lesson in molecular therapeutics. Ochsner J 7:61–64Google Scholar
- Presek P, Glossmann H, Eigenbrodt E, Schoner W, Rübsamen H, Friis RR, Bauer H (1980) Similarities between a phosphoprotein (pp60src)-associated protein kinase of Rous sarcoma virus and a cyclic adenosine 3′:5′-monophosphate independent protein kinase that phosphorylates pyruvate kinase type M2. Cancer Res 40:1733–1741PubMedGoogle Scholar
- Rosa JL, Casaroli-Marano RP, Buckler AJ, Vilaro S, Barbacid M (1996) p619, a giant protein related to the chromosome condensation regulator RCC1, stimulates guanine nucleotide exchange on ARF1 and Rab proteins. EMBO J 15:4262–4273; Corrigendum 1996: EMBO J 15:5738Google Scholar
- Staal GEJ, Rijksen G (1991) Pyruvate kinase in selected human tumors. In: Pretlow TG, Pretlow TP (eds) Biochemical and molecular aspects of selected cancers. Academic Press, San Diego, pp 313–337Google Scholar
- Warburg O, Poesener K, Negelein E (1924) Über den Stoffwechsel der Karzinomzellen. Biochem Z 152:309–344Google Scholar