RT Journal Article
SR Electronic
T1 The oncogene FOXQ1 is a selective activator of Wnt/β-catenin signalling
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.17.476620
DO 10.1101/2022.01.17.476620
A1 Giulia Pizzolato
A1 Lavanya Moparthi
A1 Simon Söderholm
A1 Claudio Cantù
A1 Stefan Koch
YR 2022
UL http://biorxiv.org/content/early/2022/01/17/2022.01.17.476620.abstract
AB The forkhead box transcription factor FOXQ1 is aberrantly induced in various cancers, and contributes to tumour growth and metastasis. It has been suggested that FOXQ1 exacerbates cancer by activating the oncogenic Wnt/β-catenin signalling pathway. However, the mode of action of FOXQ1 in the Wnt pathway remains to be resolved. Here, we report that FOXQ1 is a bimodal transcriptional activator of Wnt target gene expression in normal and cancer cells. Using co-immunoprecipitation, proximity proteomics, and reporter assays, we show that FOXQ1 engages the Wnt transcriptional complex to promote gene expression via TCF/LEF transcription factors. In parallel, FOXQ1 differentially regulates the expression of Wnt target genes independently of β-catenin and TCF/LEFs, which is facilitated by spatially separated activator and repressor domains. Our results suggest that FOXQ1 is a novel component of the Wnt transcriptional complex that reinforces and specifies Wnt signalling in a context-dependent manner.Competing Interest StatementThe authors have declared no competing interest.