Cancer Metabolism

Author: Gianpiero Pescarmona
Date: 22/06/2007

Description

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

transketolase cancer

Papers transketolase and cancer

Pyruvate Dehydrogenase

DCA
BUYDCA

p53

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

FRP4

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

  • LDHC

LDHC Hypoxia

da leggere

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.

EGLN1_HUMAN

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

Comments
2008-03-31T05:59:11 - Gianpiero Pescarmona

ghi,
>>
>> mi sembra opportuno segnalarvi il colloquium di martedì 19 gennaio
>> alle ore 14.30 in Aula Magna con Chris Sander del Memorial Sloan
>> Kettering Cancer Center (MSKCC) di New York, promosso dal Politecnico
>> di Torino e dalla Human Genetics Foundation (HuGeF) - Torino.
>>
>> La presentazione avrà carattere generale e verterà sul problema
>> dell'identificazione delle reti di interazioni biologiche che
>> descrivono il comportamento di cellule tumorali.
>>
>> Chris Sander dirige il settore di biologia computazionale e dei
>> sistemi del Memorial Sloan-Kettering Cancer Center di New York ed e'
>> professore congiunto presso le Università di Rockefeller e Cornell.
>> Precedentemente, è stato il fondatore del Programma di Biocomputing al
>> Laboratorio Europeo di Biologia Molecolare (EMBL) di Heidelberg.
>> Insieme a Gay Brader dell'Universita' di Toronto, Sander dirige il
>> progetto "Pathways Commons information Resource and bioPAX pathway
>> ontology". Ha inoltre promosso e partecipa a numerose collaborazioni
>> internazionali di ricerca sulla biologia dei tumori: in particolare
>> l'iniziativa Stand Up To Cancer (SU2C), il Cancer Genome Atlas (TCGA)
>> e il consorzio internazionale ICGC (International Cancer Genome
>> Consortium).
>>
>> Invitandovi a partecipare e a coinvolgere quanti riterrete interessati
>> non solo in Ateneo, vi saluto cordialmente.
>>
>>
>> Il Rettore
>> Francesco Profumo
>>
>>
>> COLLOQUIUM, Materdi' 19, ore 14.30, Aula Magna Politecnico di Torino
>>
>> TITLE: Systems Biology of Cancer Cells
>>
>> ABSTRACT: We present a novel method for deriving network models from
>> molecular profiles of perturbed cellular systems. The network models
>> aim to predict quantitative outcomes of combinatorial perturbations,
>> such as drug pair treatments or multiple genetic alterations.
>> Mathematically, we represent the system by a set of nodes,
>> representing molecular concentrations or cellular processes, a
>> perturbation vector and an interaction matrix. After perturbation, the
>> system evolves in time according to differential equations with
>> built-in non-linearity, similar to Hopfield networks, capable of
>> representing epistasis and saturation effects. For a particular set of
>> experiments, we derive the interaction matrix by minimizing a
>> composite error function, aiming at accuracy of prediction and
>> simplicity of network structure. To evaluate the predictive potential
>> of the method we performed drug pair treatment experiments in a human
>> breast cancer cell line (MCF7) with observation of phospho-proteins
>> and cell cycle markers. The best derived network model rediscovered
>> known interactions and contained interesting predictions.
>> Possible applications of the combinatorial perturbation approach
>> include the discovery of regulatory interactions, the design of
>> targeted combination therapies, and the engineering of molecular
>> biological networks.
>>

Scoperto il segreto immortalità del cancro

Si tratta di una classe di piccole molecole di Rna conosciute come microRna. A isolarle in laboratorio per inchiodarle alle loro responsabilità è uno studio dell'università di Roma 'La Sapienza', II Facoltà di medicina e chirurgia, che ha coinvolto altri atenei come quello di Ferrara e l'Ohio State University. La ricerca, che ha guadagnato le pagine della rivista 'Cancer Cell', è stata finanziata dall'Associazione italiana ricerca sul cancro (Airc) e dall'Istituto superiore di sanità (Iss), e ha evidenziato un nuovo meccanismo alla base della trasformazione tumorale. Lo studio ha dimostrato che queste piccole molecole regolatrici risultano alterate in gran parte dei carcinomi gastrici, "ma, come dimostrano altre due ricerche pubblicate in questo stesso mese su Cell e Nature - spiega Andrea Vecchione, a capo dello studio e ricercatore presso la II Facoltà di medicina e chirurgia dell'ospedale Sant'Andrea di Roma - è alla base di un gran numero di carcinomi, di certo non solo delle neoplasie dello stomaco". I microRna, "essendo alla base di queste due importanti funzioni cellulari - sottolinea il ricercatore - rappresentano ottimi target su cui investire per ottenere un miglior trattamento personalizzato di questo tipo di tumori". Sembrerebbero aprire, dunque, nuovi spiragli nella lotta contro il cancro. Ma questo tipo di ricerche "risultano molto costose e d estremamente faticose, prevedono l'impegno di risorse economiche ingenti e di risorse umane altamente motivate". Per questo motivo, Vecchione ringrazia l'Airc e l'Iss che hanno "creduto nel progetto e nelle capacità dell'equipe di studio, finanziando questa ricerca che ha portato eccellenti risultati scientifici. La speranza di tutti - dice - è che anche altre istituzioni pubbliche e private seguano quest'esempio e aumentino i finanziamenti destinati alla ricerca scientifica che rappresenta la vera forza di un paese sviluppato".

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