Decreased fructose-1,6-bisphosphatase-2 expression promotes glycolysis and growth in gastric cancer cells.
BACKGROUND
Increasing evidence suggests that cancer is a metabolic disease. Here, we investigated the potential role of fructose-1,6-bisphosphatase-2 (FBP2), the enzyme that catalyses the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and inorganic phosphate in glucose metabolism, in gastric cancer (GC) development.


RESULTS
Our data indicated that FBP2 was downregulated in GC tissues (86.2%, 100/116), and absent or low FBP2 expression in GC tissues was correlated with poor survival of GC patients (P = 0.019). Conversely, ectopic expression of FBP2 in GC cells activated AMP-activated protein kinase (AMPK) signalling, inhibited the Akt-mTOR pathway, suppressed glucose metabolism, enhanced apoptosis, and reduced cell proliferation. Bisulphite genomic sequencing (BGS) in gastric cancer cell lines revealed that the FBP2 promoter region was densely methylated, and treatment of GC cells with the demethylation reagent, 5-aza-2-deoxycytidine (5-Aza), led to an increase in FBP2 expression. Importantly, forced expression of FBP2 abrogated tumour formation of these GC cells in nude mice.


CONCLUSIONS
Our results indicate that FBP2 does negatively regulate cell growth, and reduced expression of FBP2 may contribute to carcinogenesis for GC. These findings suggest that restoration of FBP2 expression can be a promising strategy for the target therapy of GC.
Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute, Beijing 100142, China. hbzhang2006@gmail.com.
He
H
Li
Juan
J
Wang
Huiyu
H
Xu
Rui
R
Xing
Yuanming
Y
Pan
Wenmei
W
Li
Jiantao
J
Cui
Hongbing
H
Zhang
Youyong
Y
Lu
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D005260:Female; D006597:Fructose-Bisphosphatase / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006019:Glycolysis; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D015999:Multivariate Analysis; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D047368:Tumor Burden
D006597:Fructose-Bisphosphatase