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

0500434 - ÚMG 2019 RIV CH eng J - Článek v odborném periodiku
Hrčkulák, Dušan - Janečková, Lucie - Láníková, Lucie - Kříž, Vítězslav - Horázná, Monika - Babošová, Oľga - Vojtěchová, Martina - Galušková, Kateřina - Šloncová, Eva - Kořínek, Vladimír
Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells.
Genes. Roč. 9, č. 9 (2018), č. článku 439. E-ISSN 2073-4425
Grant CEP: GA ČR GA15-25100S; GA MŠMT LO1419; GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) LM2015062
Institucionální podpora: RVO:68378050
Klíčová slova: colorectal cancer * conditional gene inactivation * epithelium * gut * organoids * tcf7l2 * tumorigenesis * Wnt signaling
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 3.331, rok: 2018

T-cell factor 4 (TCF4), together with beta-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.
Trvalý link: http://hdl.handle.net/11104/0292514