Fructose induces transketolase flux to promote pancreatic cancer growth.
Carbohydrate metabolism via glycolysis and the tricarboxylic acid cycle is pivotal for cancer growth, and increased refined carbohydrate consumption adversely affects cancer survival. Traditionally, glucose and fructose have been considered as interchangeable monosaccharide substrates that are similarly metabolized, and little attention has been given to sugars other than glucose. However, fructose intake has increased dramatically in recent decades and cellular uptake of glucose and fructose uses distinct transporters. Here, we report that fructose provides an alternative substrate to induce pancreatic cancer cell proliferation. Importantly, fructose and glucose metabolism are quite different; in comparison with glucose, fructose induces thiamine-dependent transketolase flux and is preferentially metabolized via the nonoxidative pentose phosphate pathway to synthesize nucleic acids and increase uric acid production. These findings show that cancer cells can readily metabolize fructose to increase proliferation. They have major significance for cancer patients given dietary refined fructose consumption, and indicate that efforts to reduce refined fructose intake or inhibit fructose-mediated actions may disrupt cancer growth.
Liu
Haibo
H
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90024, USA.
Huang
Danshan
D
McArthur
David L
DL
Boros
Laszlo G
LG
Nissen
Nicholas
N
Heaney
Anthony P
AP
D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004790:Enzyme Induction / Q000187:drug effects; D005632:Fructose / Q000378:metabolism / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D018197:Hepatoblastoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009696:Nucleic Acids / Q000096:biosynthesis; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D010427:Pentose Phosphate Pathway; D011687:Purines / Q000096:biosynthesis; D014174:Transketolase / Q000096:biosynthesis / Q000378:metabolism*
D009696:Nucleic Acids; D011687:Purines; D005632:Fructose; D014174:Transketolase; D005947:Glucose; C030985:purine