Reviews Cancer metabolism
Metabolic reprogramming in tumor cells.
The alteration of bioenergetic pathways in tumor cells is evident from their increased glucose uptake
- (a) through glycolysis
- (b), the intermediate metabolites of which are also shuttled into biosynthetic pathways (synthesis of nucleic acids from glucose 6-phosphate through the pentose phosphate pathway
- ©, amino acids from glycerate 3-phosphate (not shown) and lipogenesis from pyruvate
- (d)) that are necessary for cell growth and proliferation. In tumor cells, pyruvate in the mitochondria is shuttled into a truncated tricarboxylic acid cycle where it is converted to acetyl-CoA by pyruvate dehydrogenase and combined with oxaloacetate for export into the cytosol as citrate for the synthesis of isoprenoids, cholesterol and fatty acids.
Open up and down arrows indicate upregulation and downregulation of enzymes, respectively. Enzymes upregulated by activation of HIF-1 are in red. Abbreviations: ACL, adenosine triphosphate citrate lyase; ADP, adenosine diphosphate; ATP, adenosine triphosphate; CA9 and CA12, carbonic anhydrases 9 and 12; CPT1A, carnitine palmitoyltransferase 1A; FASN, fatty acid synthase; G6P, glucose 6-phosphate; GLUT1,3,4, glucose transporter 1, 3 and 4; GSH, glutathione; HIF-1, hypoxia-inducible factor 1; HK1,2, hexokinase1 and 2; LAT1, L-type amino acid transporter 1; LDH-A, lactate dehydrogenase A; MCT4, monocarboxylate transporter 4; M2-PK, pyruvate kinase isoform M2; NAD+, nicotinamide adenine dinucleotide oxidized; NADH, nicotinamide adenine dinucleotide reduced; NADPH, nicotinamide adenine dinucleotide phosphate; NHE1, Na+/H+ exchanger 1; OAA, oxaloacetate; OXPHOS, oxidative phosphorylation; PDH, pyruvate dehydrogenase; PDK1, pyruvate dehydrogenase kinase 1; PFK2, phosphofructokinase 2; PGM, phosphoglycerate mutase; PI3K, phosphatidylinositol 3-kinase; PPP, pentose phosphate pathway; TLK1, transketolase 1; VDAC, voltage-dependent anion channel. Reproduced with permission from (How close is the bench to the bedside? Metabolic profiling in cancer 2009).
Nutrient transporters in cancer: Relevance to Warburg hypothesis and beyond. 2008
Tumour metabolism: Shifting the balance 2006
Cancer Cell Metabolism: Warburg and Beyond 2008
Metabolism: Warburg effect revisited 2008
Mitochondrial tumour suppressor genes by Ian Tomlinson
Reviews Brain Cancer metabolism
Papers transketolase and cancer
Upregulation of glycolysis, the anaerobic breakdown of glucose to produce ATP, occurs in almost every tumour. Paul Hwang and colleagues propose that such a widespread metabolic alteration must be stimulated by a pathway with similarly widespread alterations in cancer, and found that p53, one of the most commonly mutated genes in human cancers, can alter the balance between glycolysis and aerobic respiration in tumour cells.
p53 regulates mitochondrial respiration 2006
p53 and metabolism 2009
p53 and starvation
p53 and respiratory chain
p53 and autophagy
p53 and oxidative stress
1. FUNCTION: Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP4 may act as a regulator of adult uterine morphology and function. Increases apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake.
2. SUBCELLULAR LOCATION: Secreted.
3. TISSUE SPECIFICITY: Expressed in mesenchymal cells. Highly expressed in the stroma of proliferative endometrium. Expressed in cardiomyocytes.
4. INDUCTION: Increased levels in failing myocardium. Up-regulated in several tumor types including ostomalacia-associated tumors and endometrial and breast carcinomas.
5. DOMAIN: The FZ domain is involved in binding with Wnt ligands (By similarity).
6. DISEASE: Associated with tumor-induced osteomalacia, a disorder in which there is an increase in renal phosphate excretion and a reduction in serum phosphate levels leading to hyperphosphaturia, hypophosphatemia and rickets.
7. SIMILARITY: Belongs to the secreted frizzled-related protein (sFRP) family.
8. SIMILARITY: Contains 1 FZ (frizzled) domain.
9. SIMILARITY: Contains 1 NTR domain.
10. SEQUENCE CAUTION: Sequence=AAH32828.1; Type=Frameshift; Positions=17;
Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment 2003
Anticancer Targets in the Glycolytic Metabolism of Tumors: A Comprehensive Review, 2011
PHD2 is a Fe(II)- and 2-oxoglutarate-dependent dioxygenase which has an absolute requirement for molecular oxygen: because of its low affinity for oxygen (Km = 250 μM, slightly above air pO2; Hirsila et al. ), PHD2 is often described as an oxygen sensor.
Genetic Evidence for High-Altitude Adaptation in Tibet,2010 Fulltext
Citrate and Isocitrate
Why isocitrate dehydrogenase attain so much attention specially in leukemia in comparison to the other cancers?,,
cancer as a pro inflammatory etc 2015:http://www.ncbi.nlm.nih.gov/pubmed/26508818