PT  - JOURNAL ARTICLE
AU  - Giulia Pizzolato
AU  - Lavanya Moparthi
AU  - Simon Söderholm
AU  - Claudio Cantù
AU  - Stefan Koch
TI  - The oncogene FOXQ1 is a selective activator of Wnt/β-catenin signalling
AID  - 10.1101/2022.01.17.476620
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.17.476620
4099  - http://biorxiv.org/content/early/2022/01/17/2022.01.17.476620.short
4100  - http://biorxiv.org/content/early/2022/01/17/2022.01.17.476620.full
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.