Glucose metabolic phenotype of pancreatic cancer

Table 3 Summary of changes in glycolysis in pancreatic ductal adenocarcinoma

Glycolytic enzyme	Encoding gene	Change in PDAC	Implicated pathways	Known inhibitors	Inhibitor effect in PDAC
Hexokinase			HIF	2-Deoxy-D-glucose
Hexokinase I	10q22	Up	mTor
Hexokinase II	2p13	Up	K-ras	3-BP[21]; Lonidamine, Everolimus	Reduced PDAC survival/induces PDAC necrosis
Hexokinase III	5q35.2	-	Akt
Glucokinase	7p15.3-p15.1
Phosphoglucose Isomerase (also known as Autocrine Motility Factor)	19q13.1	Up	HIF; Apoptosis	Insulin-like growth factor binding protein-3; Herceptin; 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole	Reduces overall cell viability and increases apoptosis rates
Phosphofructokinase			HIF	Aurintricarboxylic acid[191]	Inhibits fatty acid synthesis in rat hepatocytes
PFK-M (muscle type)	12q13.3	Down
PFK-L (liver type)	21q22.3	Up
PFK-P (platelet type)	10p15.3-p15.2	Up
Aldolase			HIF	3-fluro-D-glucose; 4-fluro-D-glucose
Aldolase-A	16p11.2	Up		3-[2-hydroxyethyl(methyl)amino]-2-quinoxalinecarbonitrile 1,4-dioxide	Reduces PDAC proliferation and tumour volume
Aldolase-B	5q22	Down
Aldolase-C	17cen-q12	Up
Triose Phosphate Isomerase	12p13	Up		2-phosphoglycolate; D-glycerol-1-phosphate[192]
Glyceraldehyde Phosphate Dehydrogenase			HIF; p53	Iodoacetate[27]; gossypol[21]	Reduces cell survival and induces necrosis. No effect on K-ras
GAPDHS	12p13	Up
GAPDHS (testes-specific)	19q13.12
Phosphoglycerate Kinase			HIF	1,3-bisphosphoglycerate[193]
PGK1	Xq13.3	Up
PGK2	6p12.3	?
Phosphoglycerate Mutase			p53	Inositol hexakisphosphate[194]
PGM-B	1p31	Up
PGM-M	4p14	Down
Enolase			c-Myc	Sodium fluoride[21]; D-tartonate; 3-aminoenolpyruvate 2-phosphate[195]
ENO1 (alpha)	1p36.2	Up
ENO2 (gamma, neuronal)	12.p13	Up
ENO3 (beta, muscle)	17pter-p11	-
Pyruvate Kinase			Tyrosine kinase
Isoform PK-M1 (liver/RBC)	1q21	-	Akt/c-Myc
Isoform PK-M2 (muscle)	15q22	Up		L-phospholactate; M2-PK-binding peptide aptamers[196]	Anti-cancer effects in animal models
Dimeric form
Tetrameric form

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