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Updated: Jul 13, 2025

Aip1p Dynamics Are Altered by the R256H Mutation in Actin
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Annexin A2 Stabilizes Oncogenic JAG1 Intracellular Domain by Inhibiting Proteasomal Degradation in Glioblastoma Cells

Seok Won Ham1,2,3, Jung Yun Kim1,2, Sunyoung Seo1,2

  • 1Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.

International Journal of Molecular Sciences
|October 14, 2023
PubMed

Insights

Annexin A2 (ANXA2) stabilizes the Jagged1 intracellular domain (JICD1), crucial for glioblastoma stem cell properties. Blocking ANXA2 interaction with JICD1 inhibits tumor growth, offering a potential therapeutic strategy for brain cancer.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Cancer Stem Cell Research

Background:

  • Glioblastoma (GBM) is an aggressive brain cancer with high mortality, often driven by relapsing cancer stem cells (CSCs).
  • The NOTCH signaling pathway is implicated in CSCs, but targeted therapies for GBM remain limited.
  • Jagged1 (JAG1) intracellular domain (JICD1) activates a NOTCH-independent pathway, promoting CSC properties.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of the JICD1 signaling pathway.
  • To identify key modulators involved in JICD1 stabilization and function.
  • To explore therapeutic strategies targeting the JICD1 pathway in GBM.

Main Methods:

  • Identification of proteins interacting with JICD1 using biochemical assays.
  • Assessment of JICD1 stability and degradation pathways.
  • Evaluation of ANXA2 knockdown effects on JICD1 signaling, CSC properties, and tumor aggressiveness in GBM models.

Main Results:

  • Annexin A2 (ANXA2) was identified as a critical protein that stabilizes JICD1.
  • ANXA2 binding prevents JICD1 proteasomal degradation mediated by HSP70/90 and CHIP.
  • ANXA2 knockdown significantly inhibited JICD1-driven GBM propagation and aggressiveness.
  • Targeting the ANXA2-JICD1 interaction suppressed JICD1-mediated CSC properties.

Conclusions:

  • ANXA2 stabilizes JICD1, maintaining the NOTCH-independent signaling pathway essential for GBM stem cell function.
  • The ANXA2-JICD1 interaction represents a potential therapeutic target for suppressing glioblastoma stem cell properties and tumor progression.
Keywords:
ANXA2GlioblastomaJAG1JICD1cancer stem cell

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