Related Experiment Video
Updated: Jun 6, 2026
05:58
Site-Specific Lysine Lactylation via Genetic Code Expansion in E. coli and Mammalian Cells
Published on: February 24, 2026
Lactylation-driven metabolic reprogramming promotes osteosarcoma malignancy via HDGF-mediated proliferation and
Shidong Hu1, Ling Wu2, Jianhua Wang3
1Department of Spine Surgery, Zhongda Hospital Southeast University, Nanjing, China.
Frontiers in Immunology
|June 5, 2026
Summary
This study reveals a new link between lactylation and hepatoma-derived growth factor (HDGF) in osteosarcoma (OS) progression. Targeting HDGF offers a promising strategy for precision therapy in OS patients.
Area of Science:
- Oncology
- Epigenetics
- Metabolic Reprogramming
Background:
- Osteosarcoma (OS) exhibits significant intratumoral heterogeneity and immune microenvironment remodeling.
- Mechanisms of metabolic reprogramming driving OS progression remain unclear.
- Lactylation, a lactate-derived epigenetic modification, is emerging as a key regulator of tumor metabolism and immunity.
Purpose of the Study:
- To investigate the role of lactylation-associated networks in osteosarcoma.
- To identify key regulators and therapeutic targets within these networks.
- To explore potential therapeutic strategies for osteosarcoma.
Main Methods:
- Integrative multi-omics approach including single-cell RNA sequencing and spatial transcriptomics.
- Machine learning-based prognostic modeling and SHapley Additive exPlanations (SHAP) for identifying key drivers.
- Experimental functional validation and virtual screening for therapeutic compounds.
Main Results:
- A distinct OS subpopulation with high lactylation, genomic instability, and stem-like properties was identified, correlating with poor prognosis.
- Hepatoma-derived growth factor (HDGF) was identified as a central regulator in the lactylation axis.
- HDGF knockdown inhibited OS cell proliferation, invasion, and tumor growth; spatial transcriptomics confirmed lactylation-HDGF colocalization.
Conclusions:
- A novel lactylation-HDGF regulatory axis promotes OS progression and influences the tumor microenvironment.
- HDGF serves as a potential prognostic biomarker and therapeutic target for osteosarcoma.
- Findings suggest new avenues for precision therapy in osteosarcoma.
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