Glucose metabolic phenotype of pancreatic cancer

Table 1 Systematic review of the literature involving glycolytic enzymes and pancreatic ductal adenocarcinoma

Glycolytic enzyme	In vitro studies		In vivo/clinical studies
	Ref.	Summary	Ref.	Summary
Hexokinase (HK)	[23-30,32,33,153-155]	Induced by hypoxia. Higher expression in PDAC than acinar cells. Suppresses mitochondrial ATP production	[31,153,156,157]	HK-2 expression suggests an unfavourable clinical outcome
Phosphoglucose isomerase (PGI)	[29,38-40,158]	Stimulates cell migration and metastatic potential. Induced by hypoxia. β-1 integrins are stimulated by PGI	[39]	Over-expression contributes to a more aggressive PDAC phenotype
Phosphofructokinase (PFK)	[11,48]	Upregulated in PDAC epithelia.
Aldolase	[49,52,54]	Overexpressed in PDAC. Induced by hypoxia. Delays apoptosis.	[52,53]	Highly expressed in PDAC where HIF-1α is constitutively expressed. Inhibition prolongs survival
Triosephosphate isomerase (TPI)	[55,56]	Overexpressed in PDAC
Glyceradehyde-3-Phosphate Dehydrogenase (G3PD)	[27,50,55,57,58,61,159]	Overexpressed in PDAC. Increases PDAC metabolic activity, and disrupts downstream apoptotic capases	[50,58]	Increased expression. Possible biomarker candidate.
Phosphoglycerate kinase (PK)	[62-66,160]	Overexpressed in PDAC. Angiogenesis promoter	[63]	No significant increase in expression in a murine model, but fivefold increase in activity.
Phosphoglycerate mutase (PGM)	[67,68]	M-isoform is under-expressed and B-isoform is over-expressed in murine models
Enolase	[55-58,69-83]	Overexpressed in PDAC. Promotes cell migration and metastasis. Biomarker candidate	[58,69,76,77,161-163]	Increased expression. Induced antibodies to enolase-alpha correlates to a better outcome
Pyruvate kinase (PK)	[108,109,117,121,122,157,164-166]	Overexpressed in PDAC. Dimeric form favours synthesis; Tetrameric form favours energy production; PK-M2 used as a tumour marker	[110,112,115,119,120,157,167,168]	M2 isoform levels correlate to tumour metastasis. HK-2 and M2 expression indicates an unfavourable clinical outcome
Lactate dehydrogenase (LDH)	[28,89,123-138,164,169-179]	Overexpressed in PDAC. Down regulated by graviola	[153,180-183]	Down regulated by graviola to reduce tumorigenicity and metastasis

HIF: Hypoxia-inducible factor; PDAC: Pancreatic ductal adenocarcinoma.