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2025 ; 16
(1
): 730
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The regulatory and synergistic effects of FBP2 and HKDC1 on glucose metabolism
and malignant progression in gastric cancer
#MMPMID41102152
Yu Z
; Li R
; Xu Q
; Liang C
; Gao J
; Yuan Z
; Zhao R
; Liang W
; Cao B
; Zhao X
; Wei B
; Li P
Cell Death Dis
2025[Oct]; 16
(1
): 730
PMID41102152
show ga
Fructose-1,6-bisphosphatase (FBPase) serves as the rate-limiting enzyme in
gluconeogenesis and can be categorized into two subtypes: FBP1 and FBP2. FBP1 has
been reported to exhibit reduced expression and impaired function in various
malignant tumors. However, there is limited research investigating the role of
FBP2 in tumorigenesis. Our results showed that the expression level of FBP2 in
gastric cancer (GC) tissues was reduced compared to that in adjacent non-tumor
tissues. Low FBP2 expression was correlated with adverse clinicopathological
characteristics and unfavorable prognosis. Overexpression of FBP2 in GC cells
resulted in a decreased expression level of hypoxia inducible factor-1? (HIF-1?),
enhanced oxidative phosphorylation, and a modest reduction in glycolytic
activity. Notably, the FBP2 has been shown to elevate the expression level of
hexokinase domain-containing protein-1 (HKDC1). Both cellular and animal studies
demonstrated that the overexpression of FBP2 or the knockdown of HKDC1 could
attenuate the malignant biological behavior of GC. Moreover, the synergistic
effect of these two approaches exerted a more potent anti-tumor response.
Overall, the synergistic effect of FBP2 and HKDC1 can suppress the progression of
GC through the promotion of oxidative phosphorylation and inhibition of
glycolysis. FBP2 and HKDC1 are anticipated to serve as novel molecular markers
for the diagnosis, targeted therapy, and prognosis of GC.
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