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©2014 Baishideng Publishing Group Co.
World J Gastroenterol. Mar 7, 2014; 20(9): 2279-2303
Published online Mar 7, 2014. doi: 10.3748/wjg.v20.i9.2279
Published online Mar 7, 2014. doi: 10.3748/wjg.v20.i9.2279
Table 1 Overexpression of lipogenic enzymes in human tumors
Enzyme name | Neoplasm type | Experimental model | Ref. |
Fatty acid synthase (FASN) | Pancreatic cancer | Human tumor tissue, cell line | [96,104,105] |
Breast carcinoma | Human tumor tissue | [5,9,166] | |
Prostate cancer | Human tumor tissue | [167] | |
Melanoma | Human tumor tissue | [168] | |
Nephroblastoma | Human tumor tissue | [169] | |
Renal cancer | Cell line | [170] | |
Endometrial carcinoma | Human tumor tissue | [12,171] | |
Colon cancer | Human tumor tissue | [11,172] | |
Ovarian neoplasms squamous cell | Human tumor tissue | [10,173] | |
Carcinoma of the lung head and neck squamous | Human tumor tissue | [174] | |
Cell carcinoma squamous cell | Human tumor tissue | [175] | |
Carcinoma of the tongue | Human tumor tissue | [176] | |
ATP citrate lyase (ACLY) | Small cell lung cancer | Cell line | [251] |
Bladder cancer | Human tumor tissue | [7] | |
Breast cancer | Cell line | [252] | |
Gastric cancer | Human tumor tissue, cell line | [253] | |
Colon cancer | Human tumor tissue | [254] | |
Prostate cancer | Human tumor tissue | [254] | |
Hepatocellular carcinoma | Human tumor tissue | [255] | |
Acetyl-CoA carboxylase (ACCA) | Prostate cancer | Human tumor tissue | [6] |
Hepatocellular carcinoma | Human tumor tissue | [255] | |
Breast carcinoma | Human tumor tissue | [256] | |
Stearoyl-CoA desaturase (SCD1) | Pancreatic cancer | SCD1 indices in patients serum | [128] |
Clear cell renal cell carcinoma | Human tumor tissue | [200] | |
Acetyl-CoA synthetase (ACS) | Colon adenocarcinoma | Human tumor tissue | [257] |
Malignant glioma | Cell line | [258] | |
Citrate synthase (CS) | Pancreatic cancer | Human tumor tissue | [19] |
Renal cell carcinoma | Human tumor tissue | [20] |
Table 2 Oncogenes and tumor suppressor genes, whose products participate in regulation of cancer cells metabolism
Oncogene/tumor suppressor | Metabolic pathway | Enzyme | Ref. |
MYC | Glucose transport | GLUT1 | [53-55] |
Glycolysis | Hexokinase 2 | ||
Phosphohexose isomerase | |||
Phosphofructokinase 1 | |||
Aldolase A | |||
3-phosphoglyceraldehyde dehydrogenase | |||
Phosphoglycerate kinase | |||
Phosphoglycerate mutase | |||
Enolase 1 | |||
Pyruvate kinase 2 | |||
Lactate dehydrogenase A | |||
Regulation of PDH | Pyruvate dehydrogenase kinase 1 | ||
Glutamine transport | Glutamine transporters ASCT2 and SN2 | ||
Glutaminolysis | Glutaminase 1 | ||
Serine hydroxymethyltransferase | |||
Pyrimidine synthesis | |||
Aminoacids metabolism | CAD | ||
Ornithine decarboxylase | |||
Lipogenesis | Fatty acid synthase | ||
p53 | Glucose transport | GLUT1 | [51,56-60] |
Glycolysis | Hexokinase 2 | ||
Fructose-2,6-bisphosphatase | |||
Phosphoglycerate mutase | |||
Oxidative phosphorylation | Cyrochrome c oxidase | ||
Glutaminolysis | Glutaminase 2 | ||
Pentose Phosphate Pathway | Glucose-6-phosphate dehydrogenase | ||
Regulation of PDH | Pyruvate dehydrogenase kinase 1 | ||
Krebs cycle | Aconitase | ||
KRAS | Glucose transport | GLUT1 | [61,73,94] |
Glycolysis | Hexokinase 2 | ||
Phosphofructokinase 1 | |||
Lactate dehydrogenase A | |||
Pentose phosphate pathway | Transketolase | ||
Hexosamine synthesis | Phosphohexose aminotransferase | ||
Glutaminolysis | Glutamate dehydrogenase | ||
Aspartate transaminase | |||
Akt/PTEN | Glucose transport | GLUT1 | [50,113-115] |
Lipogenesis | FASN |
Table 3 Oncogenes and tumor suppressor genes whose products alter the metabolism of pancreatic cancer cells
Gene | Protein | Mechanism of alteration in PDAC | Regulated processes in PDAC | Alteration in PDAC | Ref. |
Oncogenes | |||||
KRAS | KRAS | Point mutations | Cell proliferation and survival, motility, glucose transport, glycolysis, hexosamine synthesis, nonoxidative pentose phosphate pathway arm, glutaminolysis | > 95% | [73,94,259-261] |
AKT | AKT | Mutations, amplification | Signal transduction, lipogenesis, glucose transport | 10%-20% | [73,79-81,262-264] |
c-erbB2 | HER2 | Overexpression amplification | Proliferation, differentiation, survival | 20%-80% | [265-268] |
Myc | MYC | Amplification overexpression | Glycolysis, glutaminolysis, PDH inhibition | 70% | [55,73,82,94,269] |
Tumor suppressor genes | |||||
TP53 | p53 | Mutation and second allele deletion | Cell cycle, apoptosis, DNA repair, glucose transport, glycolysis, lipogenesis, ppp oxidative arm, glutaminolysis | 50%-80% | [270-273] |
Smad4/DPC4 | SMAD4 | Homozygous deletion, mutation and second allele deletion | Cell cycle, TGF-β signaling | 55% | [274-276] |
STK/LKB1 | LKB1 | Homozygous deletion, mutation and second allele deletion | Apoptosis, lipogenesis, energy production, protein synthesis | 5% | [277-279] |
CDKN2A/p16 | p16 | Homozygous deletion, mutation, hypermethylation | Cell cycle | 95% | [280-282] |
PTEN | PTEN | Hypermethylation, inhibition by miRNA | PI3K/AKT signaling pathway | 30%-70% | [79,283,284] |
Table 4 Most common genetic alterations observed in different types of human pancreatic cancers
Type of pancreatic cancer | Gene affected | Ref. |
Pancreatic ductal adenocarcinoma (PDAC) | KRAS, AKT, MYC, TP53, SMAD4, CDKN2A, PTEN | [55,63,64,73,78,79,94,269,284-287] |
(90% of all pancreatic cancers) | ||
Acinar cell carcinoma (ACCA) | APC/β-catenin (CTNNB1), BRCA2, BCL10 | [288-290] |
(< 1% of all pancreatic cancers) | ||
Adenosquamous carcinoma (ASC) | TP53, CDKN2A, KRAS, E-cadherin, | [291,292] |
(< 1% of all pancreatic cancers) | ||
Intraductal papillary mucinous neoplasm (IPNM) | GNAS, KRAS, RNF4, STK11/LKB1, MUC1, MUC2, hTERT, COX2, Shh | [278,293,294] |
(1%-3% of all pancreatic cancers) | ||
Mucinous cystic neoplasm (MCN) | KRAS, RNF4, TP53, CDKN2A | [295] |
(< 1% of all pancreatic cancers) | ||
Serous cystadenoma (SCN) | VHL | [296] |
(< 1% of all pancreatic cancers) | ||
Solid-pseudopapillary neoplasm (SPN) | APC/β-catenin (CTNNB1), E-cadherin | [297,298] |
(1%-2% of all pancreatic cancers) | ||
Pancreatic neuroendocrine tumors (PanNET) | DAXX, ATRX, MEN1, TSC2, PTEN, PI3KCA, CHGA, CHGB, mTOR | [299-302] |
(2%-5% of all pancreatic cancers) |
Table 5 Lipogenic enzyme inhibitors that can be used as potential antitumor drugs
Enzyme name | Inhibitor | Type of neoplasm | Ref. |
Fatty acid synthase (FASN) | Cerulenin | Breast cancer, | [303] |
ovarian cancer | [304] | ||
C75 | Breast cancer | [216] | |
Pancreatic cancer | [232] | ||
Epigallocatechin-3-gallate (EGG) | Prostate cancer | [228] | |
C93 | Lung cancer | [305] | |
Ovarian cancer | [306] | ||
Luteolin | Breast cancer, ovarian cancer | [228] | |
Pancreatic cancer | [232] | ||
Orlistat | Prostate cancer | [307] | |
ATP citrate lyase (ACLY) | SB-204990 hydroxycitrate | Lung cancer | [308] |
Brest cancer | [18] | ||
Pancreatic cancer | [101] | ||
Acetyl-CoA carboxylase (ACCA) | Soraphen A TOFA | Prostate cancer | [309] |
Lung cancer, colon cancer | [310] | ||
Stearoyl-CoA desaturase (SCD1) | CVT-11127 TOFA | Lung cancer | [222] |
Colon cancer | [225] | ||
Acetyl-CoA synthetase (ACS) | Triacsin c | Various cancers cell lines | [311] |
- Citation: Swierczynski J, Hebanowska A, Sledzinski T. Role of abnormal lipid metabolism in development, progression, diagnosis and therapy of pancreatic cancer. World J Gastroenterol 2014; 20(9): 2279-2303
- URL: https://www.wjgnet.com/1007-9327/full/v20/i9/2279.htm
- DOI: https://dx.doi.org/10.3748/wjg.v20.i9.2279