Metabolic reprogramming in pancreatic cancer (WP5220)

Homo sapiens

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).

Authors

Maria van de Meent , Martina Summer-Kutmon , and Eric Weitz

Activity

last edited

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Organisms

Homo sapiens

Communities

CPTAC

Annotations

Pathway Ontology

hexosamine biosynthetic pathway pancreatic cancer pathway altered lipid metabolic pathway citric acid cycle pathway pentose phosphate pathway altered citric acid cycle pathway

Disease Ontology

pancreatic cancer

Participants

Label Type Compact URI Comment
D-Ribulose 5-phosphate Metabolite chebi:17363
cholesterol esters Metabolite chebi:17002
BCKA Metabolite chebi:191197 Branched-chain keto acid (BCKA)
D-Ribose 5-phosphate Metabolite chebi:17797
NADPH Metabolite chebi:16474
lactate Metabolite chebi:24996
NEAA Metabolite wikidata:Q9150056 Full name: Non-Essential Amino Acids
D-Fructose 1,6-bisphosphate Metabolite chebi:16905
UDP-GlcNAc Metabolite chebi:16264 Full name: UDP-N-acetyl-D-glucosamine
glucose Metabolite chebi:17234
fatty acids Metabolite chebi:35366
Aspartic acid Metabolite chebi:22660
NADP+ Metabolite chebi:18009
D-Xylulose 5-phosphate Metabolite chebi:16332
D-Fructose 6-phosphate Metabolite chebi:15946
LDL Metabolite chebi:39026
citrate Metabolite chebi:133748
S-acetyl-CoA Metabolite chebi:15351
Oxaloacetic acid Metabolite chebi:30744
AcGlcN1P Metabolite chebi:7125 Full name: N-Acetyl-D-glucosamine 1-phosphate
BCAA Metabolite chebi:22918 Branched chain amino acids (Leu, Ile, Val)
cholesterol Metabolite chebi:16113
glutamine Metabolite chebi:28300
glutamate Metabolite chebi:14321
Oxoglutaric acid Metabolite chebi:30915
D-glucosamine 6-phosphate Metabolite chebi:58725
pyruvate Metabolite chebi:15361
succinyl-CoA Metabolite chebi:15380
malates Metabolite chebi:25115
HMG-CoA Metabolite chebi:15467
AcGlcN6P Metabolite chebi:15784 Full name: N-acetyl-D-glucosamine 6-phosphate
alpha-D-Glucose 6-phosphate Metabolite chebi:17665
PFKL Protein uniprot:P17858 ATP-dependent 6-phosphofructokinase, liver type
MDH1 Protein uniprot:P40925 Malate dehydrogenase, cytoplasmic
CARM1 Protein uniprot:Q86X55 Histone-arginine methyltransferase CARM1
HK2 Protein uniprot:P52789 Hexokinase-2
SOAT1 Protein uniprot:P35610 Sterol O-acyltransferase 1
GPT Protein uniprot:P24298 Alanine aminotransferase 1
SLC16A4 Protein uniprot:O15374 Monocarboxylate transporter 5
SLC43A1 Protein uniprot:O75387 Large neutral amino acids transporter small subunit 3
PGM3 Protein uniprot:O95394 Phosphoacetylglucosamine mutase
KRAS Protein uniprot:P01116
HK1 Protein uniprot:P19367 Hexokinase-1
HMGCS2 Protein uniprot:P54868 Hydroxymethylglutaryl-CoA synthase, mitochondrial
GFPT1 Protein uniprot:Q06210 Glutamine-fructose-6-phosphate aminotransferase [isomerizing] 1
PKM Protein uniprot:P14618 Pyruvate kinase PKM
SLC2A1 Protein uniprot:P11166 Solute carrier family 2, facilitated glucose transporter member 1
LDHA Protein uniprot:P00338 L-lactate dehydrogenase A chain
CS Protein uniprot:O75390 Citrate synthase, mitochondrial
ACLY Protein uniprot:P53396 ATP-citrate synthase
GLS2 Protein uniprot:Q9UI32 Glutaminase liver isoform, mitochondrial
GOT1 Protein uniprot:P17174 Aspartate aminotransferase, cytoplasmic
PDHA1 Protein uniprot:P08559 Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
BCKDHA Protein uniprot:P12694 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial
GLUD1 Protein uniprot:P00367 Glutamate dehydrogenase 1, mitochondrial
DLD Protein uniprot:P09622 Dihydrolipoyl dehydrogenase, mitochondrial
ME1 Protein uniprot:P48163 NADP-dependent malic enzyme
RPIA Protein uniprot:P49247 Ribose-5-phosphate isomerase
GNPNAT1 Protein uniprot:Q96EK6 Glucosamine 6-phosphate N-acetyltransferase
SLC16A1 Protein uniprot:P53985 Monocarboxylate transporter 1
GOT2 Protein uniprot:P00505 Aspartate aminotransferase, mitochondrial
HMGCR Protein uniprot:P04035 3-hydroxy-3-methylglutaryl-coenzyme A reductase
FASN Protein uniprot:P49327 Fatty acid synthase
UAP1 Protein uniprot:Q16222 UDP-N-acetylhexosamine pyrophosphorylase
DLAT Protein uniprot:P10515 Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
PDHB Protein uniprot:P11177 Pyruvate dehydrogenase E1 component subunit beta, mitochondrial
SLC1A5 Protein uniprot:Q15758 Neutral amino acid transporter B(0)
LDLR Protein uniprot:P01130 Low-density lipoprotein receptor
RPE Protein uniprot:Q96AT9 Ribulose-phosphate 3-epimerase
GPI Protein uniprot:P06744 Glucose-6-phosphate isomerase
BCAT2 Protein uniprot:O15382 Branched-chain-amino-acid aminotransferase, mitochondrial
p53 Protein uniprot:P04637
SLC7A5 Protein uniprot:Q01650 Large neutral amino acids transporter small subunit 1
PDHX Protein uniprot:O00330 Pyruvate dehydrogenase protein X component, mitochondrial

References

  1. Metabolism of pancreatic cancer: paving the way to better anticancer strategies. Qin C, Yang G, Yang J, Ren B, Wang H, Chen G, et al. Mol Cancer. 2020 Mar 2;19(1):50. PubMed Europe PMC Scholia
  2. Reprogramming of Amino Acid Metabolism in Pancreatic Cancer: Recent Advances and Therapeutic Strategies. Xu R, Yang J, Ren B, Wang H, Yang G, Chen Y, et al. Front Oncol. 2020 Sep 29;10:572722. PubMed Europe PMC Scholia
  3. The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives. Wang S, Zheng Y, Yang F, Zhu L, Zhu XQ, Wang ZF, et al. Signal Transduct Target Ther. 2021 Jul 5;6(1):249. PubMed Europe PMC Scholia
  4. The biological role of metabolic reprogramming in pancreatic cancer. Suzuki T, Otsuka M, Seimiya T, Iwata T, Kishikawa T, Koike K. MedComm (2020). 2020 Nov 5;1(3):302–10. PubMed Europe PMC Scholia