Metabolic reprogramming in pancreatic cancer (Homo sapiens)

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3KRAS / TP53MITOCHONDRIAPPPLegendPANCREATIC CANCER CELLHBPcholesterol estersPFKLD-Ribose 5-phosphateMDH1NADPHlactateCARM1HK2SOAT1GPTNEAAD-Fructose 1,6-bisphosphateUDP-GlcNAcSLC16A4SLC43A1glucosePGM3KRAS1, 3, 4fatty acidsglucoseHK1Aspartic acidNADP+lactateD-Xylulose 5-phosphateD-Fructose 6-phosphateLDLHMGCS2GFPT1PKMBCKAcitrateSLC2A1S-acetyl-CoALDHAAspartic acidCSOxaloacetic acidcitrateAcGlcN1PBCAAACLYBCAAcholesterolBCAAGLS2TCA cycleGOT1glutamineS-acetyl-CoAglutamatePDHA1Oxoglutaric acidBCKDHAGLUD1DLDOxoglutaric acidD-glucosamine 6-phosphateNADP+ME1NADPHpyruvateOxaloacetic acidsuccinyl-CoARPIAmalatesKRAS1, 3, 4glutamateGNPNAT1KRAS1, 3, 4SLC16A1KRASGOT24HMGCRKRAS2, 4FASNKRAS1, 3, 4GLUD1UAP1KRAS4DLATKRASPDHB1, 4SLC1A5LDLRKRAS4RPEKRAS4GPIOxoglutaric acidKRASHMG-CoA2, 4BCAT2TP533glutamineTP53AcGlcN6P2SLC7A5PDHXalpha-D-Glucose 6-phosphateTP531KRAS2, 4KRAS2, 4KRAS2


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
ACLYGeneProductENSG00000131473 (Ensembl)
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)
BCAT2GeneProductENSG00000105552 (Ensembl)
BCKAMetaboliteBranched-chain keto acids (KIV, KMV, KIC)
BCKDHAGeneProductENSG00000248098 (Ensembl)
CARM1GeneProductENSG00000142453 (Ensembl)
CSGeneProductENSG00000062485 (Ensembl)
D-Fructose 1,6-bisphosphateMetaboliteCHEBI:16905 (ChEBI)
D-Fructose 6-phosphateMetaboliteCHEBI:15946 (ChEBI)
D-Ribose 5-phosphateMetaboliteCHEBI:17797 (ChEBI)
D-Xylulose 5-phosphateMetaboliteCHEBI:16332 (ChEBI)
D-glucosamine 6-phosphateMetaboliteCHEBI:58725 (ChEBI)
DLATGeneProductENSG00000150768 (Ensembl)
DLDGeneProductENSG00000091140 (Ensembl)
FASNGeneProductENSG00000169710 (Ensembl)
GFPT1GeneProductENSG00000198380 (Ensembl)
GLS2GeneProductENSG00000135423 (Ensembl)
GLUD1GeneProductENSG00000148672 (Ensembl)
GNPNAT1GeneProductENSG00000100522 (Ensembl)
GOT1GeneProductENSG00000120053 (Ensembl)
GOT2GeneProductENSG00000125166 (Ensembl)
GPIGeneProductENSG00000105220 (Ensembl)
GPTGeneProductENSG00000167701 (Ensembl)
HK1GeneProductENSG00000156515 (Ensembl)
HK2GeneProductENSG00000159399 (Ensembl)
HMG-CoAMetaboliteCHEBI:15467 (ChEBI)
HMGCRGeneProductENSG00000113161 (Ensembl)
HMGCS2GeneProductENSG00000134240 (Ensembl)
KRASGeneProductENSG00000133703 (Ensembl)
LDHAGeneProductENSG00000134333 (Ensembl)
LDLMetaboliteCHEBI:39026 (ChEBI)
LDLRGeneProductENSG00000130164 (Ensembl)
MDH1GeneProductENSG00000014641 (Ensembl)
ME1GeneProductENSG00000065833 (Ensembl)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteHMDB00221 (HMDB)
NEAAMetaboliteFull name: Non-Essential Amino Acids
Oxaloacetic acidMetaboliteCHEBI:30744 (ChEBI)
Oxoglutaric acidMetaboliteCHEBI:30915 (ChEBI)
PDHA1GeneProductENSG00000131828 (Ensembl)
PDHBGeneProductENSG00000168291 (Ensembl)
PDHXGeneProductENSG00000110435 (Ensembl)
PFKLGeneProductENSG00000141959 (Ensembl)
PGM3GeneProductENSG00000013375 (Ensembl)
PKMGeneProductENSG00000067225 (Ensembl)
RPEGeneProductENSG00000197713 (Ensembl)
RPIAGeneProductENSG00000153574 (Ensembl)
S-acetyl-CoAMetaboliteCHEBI:15351 (ChEBI)
SLC16A1GeneProductENSG00000155380 (Ensembl)
SLC16A4GeneProductENSG00000168679 (Ensembl)
SLC1A5GeneProductENSG00000105281 (Ensembl)
SLC2A1GeneProductENSG00000117394 (Ensembl)
SLC43A1GeneProductENSG00000149150 (Ensembl)
SLC7A5GeneProductENSG00000103257 (Ensembl)
SOAT1GeneProductENSG00000057252 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
UAP1GeneProductENSG00000117143 (Ensembl)
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)
pyruvateMetaboliteCHEBI:15361 (ChEBI)
succinyl-CoAMetaboliteCHEBI:15380 (ChEBI)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
AcGlcN1PUDP-GlcNAcmim-conversion13510 (Rhea)
AcGlcN6PAcGlcN1Pmim-conversion23806 (Rhea)
Aspartic acidOxaloacetic acidmim-conversion21825 (Rhea)
BCAABCAAArrow29704 (Rhea)
BCAABCKAmim-conversionR-HSA-70724 (Reactome)
D-Fructose 6-phosphateD-Fructose 1,6-bisphosphatemim-conversion16110 (Rhea)
D-Fructose 6-phosphateD-glucosamine 6-phosphatemim-conversion13238 (Rhea)
D-glucosamine 6-phosphateAcGlcN6Pmim-conversion10293 (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-Xylulose 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)
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