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Updated: Aug 6, 2025

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
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Published on: February 28, 2017

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Notch activation promotes bone metastasis via SPARC inhibition in adenoid cystic carcinoma

Ye Zhang1,2,3, Xiaoxiao Liu1,2,3, Lijing Zhu1,2,3

  • 1Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.

Oral Diseases
|March 23, 2023
PubMed
Abstract

Insights

Notch pathway activation in adenoid cystic carcinoma (AdCC) promotes bone metastasis by inhibiting SPARC. SPARC shows potential as a therapeutic target and prognostic biomarker for AdCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Adenoid cystic carcinoma (AdCC) is prone to bone metastasis.
  • The Notch signaling pathway plays a role in cancer progression.
  • SPARC (secreted protein acidic and rich in cysteine) is implicated in bone remodeling.

Purpose of the Study:

  • To investigate the role of Notch signaling pathway dysregulation in AdCC bone metastasis.
  • To determine if SPARC is a potential therapeutic target in AdCC with Notch dysregulation.

Main Methods:

  • Retrospective study of 144 AdCC patients.
  • RNA-sequencing and immunohistochemistry on AdCC samples.
  • In vitro assays assessing cell proliferation, migration, and osteoclast differentiation in NICD-overexpressing cells.

Main Results:

  • Notch pathway activation correlated with down-regulation of SPARC in AdCC.
  • Overexpression of Notch intracellular domain (NICD) promoted AdCC cell growth, migration, and osteoclast differentiation.
  • Exogenous SPARC partially reversed the pro-metastatic effects of NICD.

Conclusions:

  • Notch activation in AdCC contributes to bone metastasis via SPARC inhibition.
  • SPARC may serve as a prognostic biomarker for AdCC.
  • SPARC represents a potential therapeutic target for AdCC with Notch pathway dysregulation.
Keywords:
SPARC inhibitionadenoid cystic carcinomabone metastasisbone resorptionnotch signalling pathway

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