Related Experiment Video

Updated: Jun 12, 2025

Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional 3D Model
08:08

Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional 3D Model

Published on: June 11, 2014

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Death-associated protein kinase 3 modulates migration and invasion of triple-negative breast cancer cells

Junkai Wang1, Anh M Tran-Huynh1,2, Beom-Jun Kim1

  • 1Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.

PNAS Nexus
|September 25, 2024
PubMed

Insights

Death-associated protein kinase 3 (DAPK3) is overexpressed in triple-negative breast cancer (TNBC), driving cell migration and invasion. Targeting the DAPK3/LUZP1 complex may offer new therapeutic strategies for TNBC.

Area of Science:

  • Molecular Oncology
  • Cancer Cell Biology
  • Biochemistry

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype with limited targeted therapies.
  • Understanding the molecular drivers of TNBC cell migration and invasion is crucial for developing effective treatments.

Purpose of the Study:

  • To identify novel molecular targets involved in TNBC progression.
  • To elucidate the role of death-associated protein kinase 3 (DAPK3) in TNBC cell migration and invasion.

Main Methods:

  • Mass spectrometry-based kinase inhibitor pull-down assay (KIPA) on patient-derived xenografts (PDXs).
  • Validation of DAPK3 protein enrichment in TNBC cell lines and tumors.
  • Genomic knockout of DAPK3 and mutational analysis.
  • Immunoprecipitation-mass spectrometry (IP-MS) to identify binding partners.

Main Results:

  • DAPK3 is significantly overexpressed in TNBC models.
  • DAPK3 knockout inhibits TNBC cell migration, invasion, and epithelial-mesenchymal transition (EMT).
  • DAPK3 inhibits desmoplakin (DSP) levels, impacting desmosome integrity.
  • LUZP1 binds to DAPK3, protecting it from proteasomal degradation, forming a DAPK3/LUZP1 complex.

Conclusions:

  • The DAPK3/LUZP1 heterodimer is a novel regulator of EMT and desmosome components.
  • This complex promotes TNBC cell migration and invasion.
  • DAPK3 and its interaction with LUZP1 represent potential therapeutic targets for TNBC.
Keywords:
DAPK3epithelial-to-mesenchymal transitioninvasionmigrationtriple-negative breast cancer

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