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Studying the Association of TKS4 and CD2AP Scaffold Proteins and Their Implications in the Partial

Anita Kurilla1, Loretta László1,2, Tamás Takács1,2

  • 1Institute of Enzymology, Research Centre for Natural Sciences, 1117 Budapest, Hungary.

International Journal of Molecular Sciences
|October 28, 2023
PubMed

Insights

This study reveals a new interaction between Tyrosine Kinase Substrate with four SH3 domains (TKS4) and CD2-associated protein (CD2AP). This protein complex influences colon cancer cell migration and epithelial-mesenchymal transition (EMT).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Colon cancer is a major global health concern, necessitating research into its invasiveness.
  • Understanding molecular factors driving colon cancer progression is crucial for developing new therapies.
  • The roles of Tyrosine Kinase Substrate with four SH3 domains (TKS4) and CD2-associated protein (CD2AP) in tumor formation were previously unclear.

Purpose of the Study:

  • To investigate the interaction between TKS4 and CD2AP.
  • To determine the interdependent effects of TKS4 and CD2AP on colon cancer oncogenic events.
  • To explore their cooperative role in cell migration and epithelial-mesenchymal transition (EMT).

Main Methods:

  • Co-immunoprecipitation-mass spectrometry to identify TKS4-CD2AP interaction.
  • Western blot, immunocytochemistry, and proximity ligation assay for interaction validation.
  • Peptide microarray to explore binding motifs; gene silencing and overexpression for functional analysis.

Main Results:

  • CD2AP was identified as a novel interacting partner of TKS4.
  • TKS4 and CD2AP form a scaffolding protein complex.
  • This complex regulates migration and EMT-related pathways in HCT116 colon cancer cells.

Conclusions:

  • This study provides the first evidence of TKS4-CD2AP protein-protein interaction in vitro.
  • Co-localization of TKS4 and CD2AP was observed in intact cells.
  • The TKS4-CD2AP complex potentially influences partial-EMT in colon cancer, impacting cell invasiveness.
Keywords:
CD2APTKS4colon cancerepithelial to mesenchymal transitionprotein–protein interactionscaffold proteins

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