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Open AccessArticle

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

1
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1117 Budapest, Hungary
2
Department of Biological Physics, Eötvös University, 1117 Budapest, Hungary
3
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA
4
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA
5
University of Kansas Cancer Centre, Kansas City, KS 66160, USA
6
Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria
7
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; https://doi.org/10.3390/cells8111343
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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