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 WeitzActivity
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Organisms
Homo sapiensCommunities
CPTACAnnotations
Pathway Ontology
hexosamine biosynthetic pathway pancreatic cancer pathway altered lipid metabolic pathway citric acid cycle pathway pentose phosphate pathway altered citric acid cycle pathwayDisease Ontology
pancreatic cancer| 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
- 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
- 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
- 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
- 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