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Open AccessArticle

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

Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1117 Budapest, Hungary
Department of Biological Physics, Eötvös University, 1117 Budapest, Hungary
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
University of Kansas Cancer Centre, Kansas City, KS 66160, USA
Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria
Department of Medical Chemistry, Semmelweis University Medical School, 1094 Budapest, Hungary
Author to whom correspondence should be addressed.
Contributed equally.
Cells 2019, 8(11), 1343;
Received: 24 July 2019 / Revised: 18 October 2019 / Accepted: 25 October 2019 / Published: 29 October 2019
(This article belongs to the Special Issue Epithelial–Mesenchymal Transition and Hallmarks of Cancer)
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. View Full-Text
Keywords: Tks4; scaffold protein; EMT; HCT116; motility; invasiveness Tks4; scaffold protein; EMT; HCT116; motility; invasiveness
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Szeder, B.; Tárnoki-Zách, J.; Lakatos, D.; Vas, V.; Kudlik, G.; Merő, B.; Koprivanacz, K.; Bányai, L.; Hámori, L.; Róna, G.; Czirók, A.; Füredi, A.; Buday, L. Absence of the Tks4 Scaffold Protein Induces Epithelial-Mesenchymal Transition-Like Changes in Human Colon Cancer Cells. Cells 2019, 8, 1343.

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