Absence of the Tks4 Scaffold Protein Induces Epithelial-Mesenchymal Transition-Like Changes in Human Colon Cancer Cells

Bálint Szeder, Júlia Tárnoki-Zách, Dóra Lakatos, Virág Vas, Gyöngyi Kudlik, Balázs Merő, Kitti Koprivanacz, László Bányai, Lilla Hámori, Gergely Róna, András Czirók, András Füredi, And László Buday

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Epithelial to mesenchymal transition (EMT) is a multipurpose process involved in wound healing, development, and certain pathological processes, such as metastasis formation. The Tks4 scaffold protein has been implicated in cancer progression; however, its role in oncogenesis is not well defined. In this study, the function of Tks4 was investigated in HCT116 colon cancer cells by knocking the protein out using the CRISPR/Cas9 system. Surprisingly, the absence of Tks4 induced significant changes in cell morphology, motility, adhesion and expression, and localization of E-cadherin, which are all considered as hallmarks of EMT. In agreement with these findings, the marked appearance of fibronectin, a marker of the mesenchymal phenotype, was also observed in Tks4-KO cells. Analysis of the expression of well-known EMT transcription factors revealed that Snail2 was strongly overexpressed in cells lacking Tks4. Tks4-KO cells showed increased motility and decreased cell-cell attachment. Collagen matrix invasion assays demonstrated the abundance of invasive solitary cells. Finally, the reintroduction of Tks4 protein in the Tks4-KO cells restored the expression levels of relevant key transcription factors, suggesting that the Tks4 scaffold protein has a specific and novel role in EMT regulation and cancer progression.

Original languageEnglish
Article number1343
Number of pages18
JournalCells
Volume8
Issue number11
DOIs
Publication statusPublished - 29 Oct 2019

Keywords

  • EMT
  • HCT116
  • invasiveness
  • motility
  • scaffold protein
  • Tks4

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