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The phosphatase CTDSPL2 promotes proliferation, invasion, metastasis and regorafenib resistance in osteosarcoma

Guannan Bai1, Shaobo Zhao1, Manli Zhao2

  • 1Department of Orthopedics, Children's Hospital, Zhejiang University School of Medicine, National Children's Regional Medical Center, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, Zhejiang Province 310052, China.

Journal of Bone Oncology
|May 12, 2025
PubMed

Insights

Researchers identified CTDSPL2 as a key gene driving osteosarcoma malignancy and resistance to regorafenib therapy. Targeting CTDSPL2 shows promise for treating advanced osteosarcoma by inhibiting tumor growth and spread.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osteosarcoma is a prevalent bone cancer in children and adolescents with poor outcomes for metastatic or recurrent cases.
  • Regorafenib is a multi-kinase inhibitor used in advanced osteosarcoma treatment, but resistance mechanisms are poorly understood.

Purpose of the Study:

  • To elucidate mechanisms of regorafenib resistance in osteosarcoma.
  • To identify novel therapeutic targets for osteosarcoma by analyzing multiomics data.

Main Methods:

  • Transcriptomics, proteomics, and phosphoproteomics were performed on regorafenib-treated osteosarcoma cell lines.
  • Differential gene expression analysis and functional assays (in vitro and clinical specimens) were conducted.
  • Immunohistochemistry was used to verify the upregulation of identified genes.

Main Results:

  • Comprehensive multiomics analysis identified CTDSPL2 as a gene potentially involved in osteosarcoma malignancy and regorafenib resistance.
  • CTDSPL2 promotes osteosarcoma cell proliferation, invasion, and metastasis while inhibiting apoptosis.
  • Knockdown of CTDSPL2 significantly reduced tumor cell growth, invasion, and metastasis.

Conclusions:

  • CTDSPL2 is an essential gene for osteosarcoma cell survival and tumor development.
  • CTDSPL2 plays a significant role in osteosarcoma progression and resistance to regorafenib.
  • CTDSPL2 represents a potential therapeutic target for osteosarcoma treatment.
Keywords:
ApoptosisCTDSPL2InvasionMetastasisOsteosarcomaProliferationRegorafenib

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