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Genes 2018, 9(9), 439; https://doi.org/10.3390/genes9090439

Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells

1
Institute of Molecular Genetics of the CAS, v. v. i., Videnska 1083, Prague 142 20, Czech Republic
2
Faculty of Science, Charles University in Prague, Albertov 6, Praha 128 43, Czech Republic
*
Authors to whom correspondence should be addressed.
Received: 3 July 2018 / Revised: 9 August 2018 / Accepted: 24 August 2018 / Published: 1 September 2018
(This article belongs to the Section Molecular Genetics and Genomics)
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Abstract

T-cell factor 4 (TCF4), together with β-catenin coactivator, functions as the major transcriptional mediator of the canonical wingless/integrated (Wnt) signaling pathway in the intestinal epithelium. The pathway activity is essential for both intestinal homeostasis and tumorigenesis. To date, several mouse models and cellular systems have been used to analyze TCF4 function. However, some findings were conflicting, especially those that were related to the defects observed in the mouse gastrointestinal tract after Tcf4 gene deletion, or to a potential tumor suppressive role of the gene in intestinal cancer cells or tumors. Here, we present the results obtained using a newly generated conditional Tcf4 allele that allows inactivation of all potential Tcf4 isoforms in the mouse tissue or small intestinal and colon organoids. We also employed the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system to disrupt the TCF4 gene in human cells. We showed that in adult mice, epithelial expression of Tcf4 is indispensable for cell proliferation and tumor initiation. However, in human cells, the TCF4 role is redundant with the related T-cell factor 1 (TCF1) and lymphoid enhancer-binding factor 1 (LEF1) transcription factors. View Full-Text
Keywords: colorectal cancer; conditional gene inactivation; epithelium; gut; organoids; TCF7L2; tumorigenesis; Wnt signaling colorectal cancer; conditional gene inactivation; epithelium; gut; organoids; TCF7L2; tumorigenesis; Wnt signaling
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Hrckulak, D.; Janeckova, L.; Lanikova, L.; Kriz, V.; Horazna, M.; Babosova, O.; Vojtechova, M.; Galuskova, K.; Sloncova, E.; Korinek, V. Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells. Genes 2018, 9, 439.

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