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Updated: May 24, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

Defining NOTCH3 target genes in ovarian cancer

Xu Chen1, Michelle M Thiaville, Li Chen

  • 1Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.

Cancer Research
|March 8, 2012
PubMed

Insights

NOTCH3 gene amplification drives ovarian and breast cancers. Researchers identified DLGAP5 as a key NOTCH3 target gene, crucial for cancer cell proliferation and cell cycle progression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Systems Biology

Background:

  • NOTCH3 gene amplification is implicated in ovarian and breast cancer progression.
  • The specific downstream targets of NOTCH3 signaling remain largely undefined.
  • Understanding NOTCH3 targets is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To identify direct target genes of NOTCH3 signaling using an integrated systems biology approach.
  • To elucidate the role of identified target genes in cancer cell proliferation and survival.
  • To define novel NOTCH3/CSL transcription factor binding motifs.

Main Methods:

  • Transcriptome analysis to identify NOTCH3-regulated genes.
  • Chromatin immunoprecipitation (ChIP)-on-chip to identify NOTCH3/CSL binding sites.
  • Integration of transcriptome and ChIP-on-chip data.
  • Functional studies involving gene silencing and enforced expression.

Main Results:

  • NOTCH3 suppression downregulated genes involved in cell-cycle regulation and nucleotide metabolism.
  • A new CSL binding motif (N1) was identified alongside the canonical motif.
  • DLGAP5 (HURP/DLG7) was identified as a critical NOTCH3 target gene, regulated by both motifs.
  • DLGAP5 silencing suppressed tumor growth and induced G(2)-M cell cycle arrest.
  • DLGAP5 overexpression partially rescued cells from NOTCH inhibition.

Conclusions:

  • Direct target genes of NOTCH3 signaling have been identified.
  • DLGAP5 is a critical mediator of NOTCH3 function in ovarian and breast cancer.
  • Targeting DLGAP5 may represent a therapeutic strategy for NOTCH3-driven cancers.

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