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Updated: May 6, 2026

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Integrative genomic and functional characterization of ADAMTS3 reveals its inflammatory regulation via NF-κB and

Ehed Muhammed Aymaz1, Meltem Alper2, Feyza Nur Sav3

  • 1İstinye University Graduate Education Institute Molecular Oncology Istanbul Turkey.

Journal of Cell Communication and Signaling
|May 5, 2026
PubMed

Insights

ADAMTS-3, an inflammation-responsive gene, is overexpressed in osteosarcoma (OS). It links inflammatory signals to extracellular matrix remodeling and tumor invasiveness, offering a potential therapeutic target for this aggressive bone cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma (OS) is an aggressive bone cancer with genomic instability and extensive extracellular matrix (ECM) remodeling.
  • The ADAMTS family of proteases is involved in tumorigenesis, but their specific roles in OS are not well understood.

Purpose of the Study:

  • To comprehensively analyze the genomic, transcriptomic, and functional roles of ADAMTS family members in osteosarcoma.
  • To investigate the specific role and regulation of ADAMTS-3 in OS.

Main Methods:

  • Analysis of TCGA datasets for copy number alterations and mRNA expression of ADAMTS genes.
  • Gene set enrichment and co-expression analyses to identify biological processes linked to ADAMTS-3.
  • Mechanistic studies on TNF-α regulation of ADAMTS-3 in OS cells.

Main Results:

  • Frequent amplification and high mRNA expression of ADAMTS4, ADAMTS12, ADAMTS16, and ADAMTS17 were observed, suggesting oncogenic roles.
  • ADAMTS-3 was significantly overexpressed in OS tissues and cell lines, correlating with inflammatory and matrix-remodeling genes (IL6, STAT3, NF-κB, MMP2, MMP9).
  • ADAMTS-3 is associated with ECM organization, immune response regulation, and epithelial-mesenchymal transition; TNF-α induces its transcription via MEK, PI3K, JNK, and NF-κB pathways.

Conclusions:

  • ADAMTS-3 is an inflammation-responsive gene in osteosarcoma.
  • ADAMTS-3 acts as a molecular bridge, connecting inflammatory signaling to ECM remodeling and tumor invasiveness.
  • ADAMTS-3 represents a potential therapeutic target for osteosarcoma.
Keywords:
ADAMTS‐3NF‐κB and STAT3 transcription factorsextracellular matrix remodelingosteosarcomatumor necrosis factor‐alpha (TNF‐α) signaling pathway

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