Metabolic reprogramming in pancreatic cancer (Homo sapiens)

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Revision as of 12:17, 21 April 2022 by Maria van de Meent (Talk | contribs)
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1221, 3, 43, 42, 42, 41, 3, 42, 41, 3, 4431, 3, 42, 441442, 41, 3, 44KRAS / p53OxidativeMITOCHONDRIAMutated KRAS / p53 PPPLegendPANCREATIC CANCER CELLHBPcholesterol estersD-Ribulose 5-phosphateα-ketoisovaleratePFKLD-Ribose 5-phosphateMDH1NADPHlactateCARM1HK2SOAT1GPTNEAAD-Fructose 1,6-bisphosphateUDP-GlcNAcSLC16A4SLC43A1glucosePGM3KRASfatty acidsglucoseHK1Aspartic acidNADP+lactateD-Xylulose 5-phosphateD-Fructose 6-phosphateLDLHMGCS2GFPT1PKMcitrateSLC2A1S-acetyl-CoALDHAAspartic acidCSOxaloacetic acidcitrateAcGlcN1PBCAAACLYBCAAcholesterolBCAAGLS2TCA cycleGOT1glutamineS-acetyl-CoAglutamatePDHA1Oxoglutaric acidBCKDHAGLUD1DLDOxoglutaric acidD-glucosamine 6-phosphateME1pyruvateOxaloacetic acidsuccinyl-CoARPIAmalatesKRASglutamateGNPNAT1KRASSLC16A1KRASGOT2HMGCRKRASFASNKRASGLUD1KRASUAP1DLATKRASPDHBSLC1A5KRASLDLRRPEKRASGPIOxoglutaric acidHMG-CoAKRASBCAT2p53glutamineAcGlcN6Pp53SLC7A5PDHXalpha-D-Glucose 6-phosphatep53KRASKRASKRASNonoxidativeα-keto-β-methylvalerateα-ketoisocaproate


Description

This pathway model displays the interactions between KRAS and TP53 mutations and pancreatic cancer cells. As a consequence of these mutations, the cell undergoes reprogramming of glucose, lipid and amino acid metabolism, thereby affecting the pentose phosphate pathway (PPP), hexosamine biosynthetic pathway (HBP) and the tricarboxylic acid (TCA) cycle. The pathway curation is largely based on Figure 2 of the review article by Wang et al. in 2021 (https://doi.org/10.1038/s41392-021-00659-4).

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Bibliography

  1. Xu R, Yang J, Ren B, Wang H, Yang G, Chen Y, You L, Zhao Y; ''Reprogramming of Amino Acid Metabolism in Pancreatic Cancer: Recent Advances and Therapeutic Strategies.''; Front Oncol, 2020 PubMed Europe PMC Scholia
  2. Wang S, Zheng Y, Yang F, Zhu L, Zhu XQ, Wang ZF, Wu XL, Zhou CH, Yan JY, Hu BY, Kong B, Fu DL, Bruns C, Zhao Y, Qin LX, Dong QZ; ''The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives.''; Signal Transduct Target Ther, 2021 PubMed Europe PMC Scholia
  3. Suzuki T, Otsuka M, Seimiya T, Iwata T, Kishikawa T, Koike K; ''The biological role of metabolic reprogramming in pancreatic cancer.''; MedComm (2020), 2020 PubMed Europe PMC Scholia
  4. Qin C, Yang G, Yang J, Ren B, Wang H, Chen G, Zhao F, You L, Wang W, Zhao Y; ''Metabolism of pancreatic cancer: paving the way to better anticancer strategies.''; Mol Cancer, 2020 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
134560view22:12, 22 July 2024EweitzClarify pathway names
134559view22:07, 22 July 2024EweitzOntology Term : 'pentose phosphate pathway' added !
134558view22:07, 22 July 2024EweitzOntology Term : 'hexosamine biosynthetic pathway' added !
134557view22:06, 22 July 2024EweitzOntology Term : 'citric acid cycle pathway' added !
122761view12:02, 11 May 2022Maria van de MeentChanged solid arrows to dashed if the step represents multiple steps.
122634view11:41, 22 April 2022Maria van de MeentAdded newly made CHEBI ID to BCKA node.
122606view12:17, 21 April 2022Maria van de MeentAdded identifiers to BCKAs and NEAA.
122604view09:21, 21 April 2022Maria van de MeentChanged KRAS and TP53 from GeneProducts to Proteins.
122543view12:48, 14 April 2022Maria van de MeentOntology Term : 'PW:0000403' removed !
122542view12:46, 14 April 2022Maria van de MeentOntology Term : 'altered lipid metabolic pathway' added !
122541view12:46, 14 April 2022Maria van de MeentOntology Term : 'altered citric acid cycle pathway' added !
122540view12:45, 14 April 2022Maria van de MeentOntology Term : 'altered amino acid metabolic pathway' added !
122539view11:39, 14 April 2022Maria van de MeentSwitched references from data node to interaction line and made changes to PPP layout.
122538view10:48, 14 April 2022Maria van de MeentChanged GeneProducts to proteins, changed dashed arrows to normal stimulation or inhibition depending on the effect, and added description to legend.
122537view09:22, 14 April 2022Mkutmonconnected lines and legend update
122507view10:23, 13 April 2022Maria van de MeentModified description
122477view16:16, 11 April 2022Maria van de MeentAdded more KRAS nodes and literature.
122476view15:18, 11 April 2022Maria van de MeentAdded more Rhea identifiers.
122461view20:51, 10 April 2022Maria van de MeentAdded missing enzymes and started adding Rhea identifiers.
122460view18:08, 10 April 2022Maria van de MeentAdded TP53 mutations and legend.
122459view14:53, 10 April 2022Maria van de MeentAdded KRAS mutations.
122458view17:54, 9 April 2022Maria van de MeentAdded more data nodes.
122447view17:14, 7 April 2022MaintBotOntology Term : 'pancreatic cancer' added !
122446view17:14, 7 April 2022MaintBotOntology Term : 'pancreatic cancer pathway' added !
122445view15:49, 7 April 2022Maria van de MeentAdded more data nodes and small layout changes.
122444view13:44, 7 April 2022Maria van de MeentNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACLYProteinP53396 (Uniprot-TrEMBL) ATP-citrate synthase
AcGlcN1PMetaboliteCHEBI:7125 (ChEBI) Full name: N-Acetyl-D-glucosamine 1-phosphate
AcGlcN6PMetaboliteCHEBI:15784 (ChEBI) Full name: N-acetyl-D-glucosamine 6-phosphate
Aspartic acidMetaboliteCHEBI:22660 (ChEBI)
BCAAMetaboliteCHEBI:22918 (ChEBI) Branched chain amino acids (Leu, Ile, Val)
BCAT2ProteinO15382 (Uniprot-TrEMBL) Branched-chain-amino-acid aminotransferase, mitochondrial
BCKDHAProteinP12694 (Uniprot-TrEMBL) 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial
CARM1ProteinQ86X55 (Uniprot-TrEMBL) Histone-arginine methyltransferase CARM1
CSProteinO75390 (Uniprot-TrEMBL) Citrate synthase, mitochondrial
D-Fructose 1,6-bisphosphateMetaboliteCHEBI:16905 (ChEBI)
D-Fructose 6-phosphateMetaboliteCHEBI:15946 (ChEBI)
D-Ribose 5-phosphateMetaboliteCHEBI:17797 (ChEBI)
D-Ribulose 5-phosphateMetaboliteCHEBI:17363 (ChEBI)
D-Xylulose 5-phosphateMetaboliteCHEBI:16332 (ChEBI)
D-glucosamine 6-phosphateMetaboliteCHEBI:58725 (ChEBI)
DLATProteinP10515 (Uniprot-TrEMBL) Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
DLDProteinP09622 (Uniprot-TrEMBL) Dihydrolipoyl dehydrogenase, mitochondrial
FASNProteinP49327 (Uniprot-TrEMBL) Fatty acid synthase
GFPT1ProteinQ06210 (Uniprot-TrEMBL) Glutamine-fructose-6-phosphate aminotransferase [isomerizing] 1
GLS2ProteinQ9UI32 (Uniprot-TrEMBL) Glutaminase liver isoform, mitochondrial
GLUD1ProteinP00367 (Uniprot-TrEMBL) Glutamate dehydrogenase 1, mitochondrial
GNPNAT1ProteinQ96EK6 (Uniprot-TrEMBL) Glucosamine 6-phosphate N-acetyltransferase
GOT1ProteinP17174 (Uniprot-TrEMBL) Aspartate aminotransferase, cytoplasmic
GOT2ProteinP00505 (Uniprot-TrEMBL) Aspartate aminotransferase, mitochondrial
GPIProteinP06744 (Uniprot-TrEMBL) Glucose-6-phosphate isomerase
GPTProteinP24298 (Uniprot-TrEMBL) Alanine aminotransferase 1
HK1ProteinP19367 (Uniprot-TrEMBL) Hexokinase-1
HK2ProteinP52789 (Uniprot-TrEMBL) Hexokinase-2
HMG-CoAMetaboliteCHEBI:15467 (ChEBI)
HMGCRProteinP04035 (Uniprot-TrEMBL) 3-hydroxy-3-methylglutaryl-coenzyme A reductase
HMGCS2ProteinP54868 (Uniprot-TrEMBL) Hydroxymethylglutaryl-CoA synthase, mitochondrial
KRASProteinP01116 (Uniprot-TrEMBL)
LDHAProteinP00338 (Uniprot-TrEMBL) L-lactate dehydrogenase A chain
LDLMetaboliteCHEBI:39026 (ChEBI)
LDLRProteinP01130 (Uniprot-TrEMBL) Low-density lipoprotein receptor
MDH1ProteinP40925 (Uniprot-TrEMBL) Malate dehydrogenase, cytoplasmic
ME1ProteinP48163 (Uniprot-TrEMBL) NADP-dependent malic enzyme
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
NEAAMetaboliteQ9150056 (Wikidata) Full name: Non-Essential Amino Acids
Oxaloacetic acidMetaboliteCHEBI:30744 (ChEBI)
Oxoglutaric acidMetaboliteCHEBI:30915 (ChEBI)
PDHA1ProteinP08559 (Uniprot-TrEMBL) Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
PDHBProteinP11177 (Uniprot-TrEMBL) Pyruvate dehydrogenase E1 component subunit beta, mitochondrial
PDHXProteinO00330 (Uniprot-TrEMBL) Pyruvate dehydrogenase protein X component, mitochondrial
PFKLProteinP17858 (Uniprot-TrEMBL) ATP-dependent 6-phosphofructokinase, liver type
PGM3ProteinO95394 (Uniprot-TrEMBL) Phosphoacetylglucosamine mutase
PKMProteinP14618 (Uniprot-TrEMBL) Pyruvate kinase PKM
RPEProteinQ96AT9 (Uniprot-TrEMBL) Ribulose-phosphate 3-epimerase
RPIAProteinP49247 (Uniprot-TrEMBL) Ribose-5-phosphate isomerase
S-acetyl-CoAMetaboliteCHEBI:15351 (ChEBI)
SLC16A1ProteinP53985 (Uniprot-TrEMBL) Monocarboxylate transporter 1
SLC16A4ProteinO15374 (Uniprot-TrEMBL) Monocarboxylate transporter 5
SLC1A5ProteinQ15758 (Uniprot-TrEMBL) Neutral amino acid transporter B(0)
SLC2A1ProteinP11166 (Uniprot-TrEMBL) Solute carrier family 2, facilitated glucose transporter member 1
SLC43A1ProteinO75387 (Uniprot-TrEMBL) Large neutral amino acids transporter small subunit 3
SLC7A5ProteinQ01650 (Uniprot-TrEMBL) Large neutral amino acids transporter small subunit 1
SOAT1ProteinP35610 (Uniprot-TrEMBL) Sterol O-acyltransferase 1
UAP1ProteinQ16222 (Uniprot-TrEMBL) UDP-N-acetylhexosamine pyrophosphorylase
UDP-GlcNAcMetaboliteCHEBI:16264 (ChEBI) Full name: UDP-N-acetyl-D-glucosamine
alpha-D-Glucose 6-phosphateMetaboliteCHEBI:17665 (ChEBI)
cholesterol estersMetaboliteCHEBI:17002 (ChEBI)
cholesterolMetaboliteCHEBI:16113 (ChEBI)
citrateMetaboliteCHEBI:133748 (ChEBI)
fatty acidsMetaboliteCHEBI:35366 (ChEBI)
glucoseMetaboliteCHEBI:17234 (ChEBI)
glutamateMetaboliteCHEBI:14321 (ChEBI)
glutamineMetaboliteCHEBI:28300 (ChEBI)
lactateMetaboliteCHEBI:24996 (ChEBI)
malatesMetaboliteCHEBI:25115 (ChEBI)
p53ProteinP04637 (Uniprot-TrEMBL)
pyruvateMetaboliteCHEBI:15361 (ChEBI)
succinyl-CoAMetaboliteCHEBI:15380 (ChEBI)
α-keto-β-methylvalerateMetaboliteCHEBI:28654 (ChEBI) Branched-chain keto acid (BCKA)
α-ketoisocaproateMetaboliteCHEBI:17865 (ChEBI) Branched-chained keto acid (BCKA)
α-ketoisovalerateMetaboliteCHEBI:11851 (ChEBI)
  • Branched-chain keto acid (BCKA)
  • Alternative name: 3-methyl-2-oxobutanoate

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
AcGlcN1PUDP-GlcNAcmim-conversion13510 (Rhea)
AcGlcN6PAcGlcN1Pmim-conversion23806 (Rhea)
Aspartic acidOxaloacetic acidmim-conversion21825 (Rhea)
BCAABCAAArrow29704 (Rhea)
BCAAα-ketoisovaleratemim-conversionR-HSA-70724 (Reactome)
D-Fructose 6-phosphateD-Fructose 1,6-bisphosphatemim-conversion16110 (Rhea)
D-Fructose 6-phosphateD-glucosamine 6-phosphatemim-conversion13238 (Rhea)
D-Ribulose 5-phosphateD-Ribose 5-phosphatemim-conversion14659 (Rhea)
D-Ribulose 5-phosphateD-Xylulose 5-phosphatemim-conversion13678 (Rhea)
D-glucosamine 6-phosphateAcGlcN6Pmim-conversion10293 (Rhea)
NADPHmim-conversion10117 (Rhea)
Oxaloacetic acidAspartic acidmim-conversion21826 (Rhea)
Oxaloacetic acidmalatesmim-conversion21434 (Rhea)
S-acetyl-CoAHMG-CoAmim-conversion10189 (Rhea)
S-acetyl-CoAcitratemim-conversion16846 (Rhea)
S-acetyl-CoAfatty acidsmim-conversion14994 (Rhea)
alpha-D-Glucose 6-phosphateD-Fructose 6-phosphatemim-conversion11817 (Rhea)
alpha-D-Glucose 6-phosphateD-Ribulose 5-phosphatemim-conversion13678 (Rhea)
cholesterolcholesterol estersmim-conversion17730 (Rhea)
citrateS-acetyl-CoAmim-conversion21162 (Rhea)
glucosealpha-D-Glucose 6-phosphatemim-conversion17826 (Rhea)
glucoseglucoseArrow60377 (Rhea)
glutamateOxoglutaric acidmim-conversion15134 (Rhea)
glutamateOxoglutaric acidmim-conversion19455 (Rhea)
glutamatemim-conversion15135 (Rhea)
glutamineglutamatemim-conversion15890 (Rhea)
glutamineglutamineArrow68237 (Rhea)
lactatelactateArrow34988 (Rhea)
lactatelactateArrow34989 (Rhea)
lactatepyruvatemim-conversion23445 (Rhea)
malatespyruvatemim-conversion18254 (Rhea)
pyruvateS-acetyl-CoAmim-conversion28043 (Rhea)
pyruvatelactatemim-conversion23446 (Rhea)
α-keto-β-methylvaleratemim-conversionR-HSA-70724 (Reactome)
α-ketoisocaproatemim-conversionR-HSA-70724 (Reactome)
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