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Cellular and Molecular Biology

ENO1 promotes cancer metastasis via stimulating metabolism reprogramming in osteosarcoma

British Journal of Cancer volume 133, pages 1625–1639 (2025)Cite this article

Subjects

Abstract

Background

This study aims to unravel the underlying mechanisms of osteosarcoma (OS) metastasis by single-cell RNA-sequencing.

Methods

Ten pediatrics OS samples were analyzed using scRNA-seq and divided into three groups: primary tumor without lung metastasis (Pri_non_MT), primary tumor with lung metastasis (Pri_MT), and lung metastasis site (MT). Candidate genes associated with metastasis were identified by bioinformatics analysis and was confirmed at mRNA and protein levels in OS tissues. The function of candidate gene was identified in vitro and in vivo. Bulk RNA sequencing was used to explore downstream mechanism after candidate gene silenced.

Results

A total of 17 cell clusters were identified. ENO1 was selected as the candidate gene and was significantly expressed in Pri_MT and MT groups. In OS tissues, ENO1 significantly overexpressed in patients with lung metastasis compared to those without. Knocking down ENO1 resulted in a marked decrease in migration and invasion in vitro and a reduction in lung metastasis in vivo. Additionally, ENO1 suppression resulted in shifting the primary ATP production pathway from glycolysis to oxidative phosphorylation.

Conclusions

Our findings highlight ENO1 as a key regulator of glycolysis and metastasis in osteosarcoma, offering a novel therapeutic target for OS treatment.

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Fig. 1: Construction of single cell atlas of osteosarcoma.
Fig. 2: T cell heterogeneity.
Fig. 3: Myeloid cell heterogeneity.
Fig. 4: NMF gene programs analysis and glucose metabolism score.
Fig. 5: Screening of the candidate genes and its expression in OS tissues.
Fig. 6: Explore the function of ENO1 in vitro.
Fig. 7: Explore the function of ENO1 in vivo.
Fig. 8: Bulk RNA sequencing analysis.

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Data availability

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the Medical Research Data Center of Fudan University.

Funding

This study was supported by the National Natural Science Foundation of China (project approval No. 82272441). Science and Technology Commission of Shanghai Municipality (CN). Grant No. 22Y11912200.

Author information

Author notes

  1. These authors contributed equally: Peng Huang, Shiwei He, Zhi Qi.

  2. These authors jointly supervised this work: Rui Dong, Gong Chen, Bo Ning.

Authors and Affiliations

  1. Children’s Hospital of Fudan University, National Children’s Medical Center Department of Orthopaedics Surgery, Shanghai, China

    Peng Huang, Zhi Qi, Yaxier Nijiati, Junfeng Wang, Zichen Lin & Bo Ning

  2. Children’s Hospital of Fudan University, National Children’s Medical Center Department of Pediatric Surgery, Shanghai, China

    Shiwei He, Rui Dong & Gong Chen

  3. Fujian Medical University, School of Public Health, Department of Population Medicine, University Town, Fujian, China

    Shiwei He

  4. Children’s Hospital of Fudan University, National Children’s Medical Center, Department of Pathology, Shanghai, China

    Yangyang Ma

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Contributions

PH and SWH participated in the design of the study and performed the data analysis, PH, ZQ and YN carried out the in vitro and vivo studies. JFW participated in the data analysis. ZCL and YYM performed part of the experiments. RD, GC and BN conceived of the study, provided the funding, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Rui Dong, Gong Chen or Bo Ning.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study protocol was approved by Children’s Hospital of Fudan University (2022-202). All experiments were performed incompliance with the relevant regulations, and all patients provided written informed consent. Besides, the animal studies were approved by the Animal Ethics Committee of Children’s Hospital of Fudan University (00036). The experiments followed the Guidelines for the Care and Use of Laboratory Animals issued by the Chinese Council on Animal Research.

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Huang, P., He, S., Qi, Z. et al. ENO1 promotes cancer metastasis via stimulating metabolism reprogramming in osteosarcoma. Br J Cancer 133, 1625–1639 (2025). https://doi.org/10.1038/s41416-025-03182-3

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