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Updated: Aug 13, 2025

In vitro Organoid Culture of Primary Mouse Colon Tumors
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Absence of Scaffold Protein Tks4 Disrupts Several Signaling Pathways in Colon Cancer Cells

Mevan Jacksi1,2, Eva Schad1, László Buday1,3

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

International Journal of Molecular Sciences
|January 21, 2023
PubMed

Insights

Deleting Tks4 protein in colorectal cancer cells significantly altered gene expression, impacting pathways beyond EGFR signaling. This suggests Tks4 plays a broader role in cellular processes and cancer development.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genomics

Background:

  • Tks4 is a scaffold protein in the EGFR pathway, influencing cell motility, development, and linked to Frank-ter Haar syndrome.
  • Loss of Tks4 induces an EMT-like process in colorectal carcinoma cells, increasing motility and EMT marker expression.

Purpose of the Study:

  • To investigate the comprehensive effects of Tks4 deletion on the gene expression profile of HCT116 colorectal carcinoma cells.
  • To identify protein-coding genes and long non-coding RNAs affected by Tks4 knockout.

Main Methods:

  • Transcriptome sequencing of wild-type and Tks4 knockout (KO) HCT116 colorectal carcinoma cells.
  • Quantitative PCR validation for selected genes with altered mRNA levels.

Main Results:

  • Significant alterations in mRNA levels of numerous protein-coding genes and long non-coding RNAs were identified in Tks4 KO cells.
  • Gene expression changes indicate a perturbation of cellular signaling pathways beyond the known EGFR pathway.

Conclusions:

  • Tks4 deletion causes widespread changes in gene expression in colorectal carcinoma cells.
  • These findings suggest Tks4 is involved in regulating diverse signal transduction pathways, extending beyond its established role in EGFR signaling.
Keywords:
EGFR signalingFrank–ter Haar syndromeTks4epithelial–mesenchymal transitiongene regulationlong non-coding RNAsignal transduction

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