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PFKP promotes oncogenesis in osteosarcoma through PI3K/HIF-1α pathway-mediated H3K18la modification
Xue Zhang1, Mingyue Guan1, Yuanyuan Wang1
1Department of Basic Medical, Jiamusi University, Jiamusi, Heilongjiang 154007, China.
Cellular Signalling
|July 9, 2026
Summary
Phosphofructokinase-platelet (PFKP) drives osteosarcoma progression by increasing lactate and protein lactylation, including histone H3 lysine 18 lactylation (H3K18la). The natural compound quercetin inhibits PFKP, offering potential therapeutic benefits for osteosarcoma.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Cancer cells preferentially use aerobic glycolysis, leading to lactate accumulation and protein lactylation, such as histone H3 lysine 18 lactylation (H3K18la).
- Phosphofructokinase-platelet (PFKP), a key enzyme in glycolysis, is upregulated in many cancers, but its role in osteosarcoma is not well understood.
Purpose of the Study:
- To investigate the role of PFKP in osteosarcoma progression.
- To elucidate the underlying molecular mechanisms.
- To explore the therapeutic potential of targeting PFKP.
Main Methods:
- Bioinformatic analysis of osteosarcoma GEO datasets.
- Gene expression analysis (RT-qPCR, Western blot, IHC).
- In vitro and in vivo functional assays (cell proliferation, migration, lactate production measurement).
- Pathway analysis (PI3K/HIF-1α), molecular docking, and compound validation (quercetin, LY294002, 2DG, CETSA).
Main Results:
- PFKP is significantly upregulated in osteosarcoma tissues and cells, correlating with disease progression.
- PFKP knockdown inhibits osteosarcoma cell proliferation, migration, lactate production, and global protein lactylation (including H3K18la).
- PFKP promotes osteosarcoma via the PI3K/HIF-1α pathway, and the natural compound quercetin binds PFKP, inhibiting its oncogenic activity and osteosarcoma cell growth.
Conclusions:
- PFKP plays a critical role in promoting osteosarcoma progression by enhancing lactate production and protein lactylation through the PI3K/HIF-1α pathway.
- Targeting PFKP, potentially with compounds like quercetin, represents a promising therapeutic strategy for osteosarcoma management.
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