The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth

By H. Christofk, M. V. Vander Heiden, M. Harris, A. Ramanathan, R. Gerszten, R. Wei, M. Fleming, Stefan Schreiber, Lewis C. Cantley. Nature, 2008

2,811 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7569b72221055030f3398c2326deaa13fd2201e1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. M. V. Vander Heiden
2. C. V. Dang
3. Navdeep S. Chandel
4. Ralph J. Deberardinis
5. G. Semenza
6. Craig B. Thompson
7. Jason W. Locasale
8. David M. Sabatini

In Molecular Biology

1. David M. Sabatini
2. Navdeep S. Chandel
3. C. V. Dang
4. M. V. Vander Heiden
5. Ralph J. Deberardinis
6. Craig B. Thompson
7. G. Semenza
8. Jason W. Locasale

Citations in the corpus

• Targeting Metabolism for Cancer Therapy (2017, background): “Paradoxically, decreased pyruvate kinase activity is associated with increased aerobic glycolysis, suggesting the activation of pyruvate kinase activity might be a way to target cancer (Christofk et al., 2008).”
• Catabolic efficiency of aerobic glycolysis: The Warburg effect revisited (2010, background): “However, the metabolic state of tumor cells itself is not a unique target for cancer chemotherapy, though individual, tumor specific isozymes may be targeted [14].”
• Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis (2010, background): “, 2008b; Jones and Thompson, 2009; Kroemer and Pouyssegur, 2008), including those that regulate glycolysis (Christofk et al., 2008; Gatenby and Gillies, 2004), glutaminedependent anaplerosis (DeBerardinis et al.”
• The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma (2009, background): “, aerobic glycolysis, which is thought to be a characteristic of tumor cells, stem cells, and cancer stem cells.(12,13) The M1 isoform is the “adult” isoform, while the M2 isoform is the corresponding “embryonic or developmental” isoform, both generated by alternate splicing from the same gene.”
• Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity (2010, background): “Tumor cells express the PKM2 isoform and inhibition of PKM2 reduces xenograft tumor growth of human lung cancer cells (23).”
• Tumor cell metabolism: cancer's Achilles' heel. (2008, background): “This indirectly modulates the activity of the cancerspecific isoform of pyruvate kinase, PKM2, which can bind to phosphotyrosine-containing peptides (Christofk et al., 2008b).”
• The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis (2011, background): “…cells Androgen stimulation of prostate cancer cells increased glucose uptake and increased lactate production in normoxia, but had no effect on oxygen consumption, showing that AR signalling does indeed stimulate aerobic glycolysis (Christofk et al, 2008; Vander Heiden et al, 2009) (Figure 2E–”
• Amplification of phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis (2012, background): “Most tumors display enhanced glucose metabolism compared to normal tissues [1-6].”
• The return of metabolism: biochemistry and physiology of the pentose phosphate pathway (2014, background): “Proliferating mammalian cells have increased levels of glycolytic enzymes, one of these is represented by PK isozymes M1/M2 (PKM1/2) (Bock & Lengauer, 2008; Christofk et al., 2008; Hitosugi et al., 2009; Bluemlein et al., 2011).”
• Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. (2011, positive): “The M2 isoform can also be inhibited as a consequence of tyrosine kinase signaling in tumor cells (Christofk et al 2008b).”
• Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation (2011, background): “Because both EGFR activation and PKM2 expression are instrumental in tumorigenesi”
• Tyrosine Phosphorylation Inhibits PKM2 to Promote the Warburg Effect and Tumor Growth (2009, methodology): “To elucidate the role of FGFR1 in phosphorylation and inhibition of PKM2 in cancer cells, we used FGFR1-expressing human lung cancer H1299 cells to generate mouse PKM2 (mPKM2) wild type, Y105F, and Y390F “rescue” cell lines as described (7) by RNA interference–mediated stable knockdown of endogenous”
• Blinded by the Light: The Growing Complexity of p53. (2009, background): “Indeed, the dependence of cancers on metabolic transformation is highlighted by mouse models of cancer in which interfering with these altered metabolic programs profoundly limits tumor cell growth (Bonnet et al., 2007; Christofk et al., 2008; Fantin et al., 2006).”