The oncogenic transcription factor FOXQ1 is a differential regulator of Wnt target genes.

Pizzolato G, Moparthi L, Söderholm S, Cantù C, Koch S

J. Cell. Sci. 135 (19) - [2022-10-01; online 2022-10-10]

The forkhead box transcription factor FOXQ1 contributes to the pathogenesis of carcinomas. In colorectal cancers, FOXQ1 promotes tumour metastasis by inducing epithelial-to-mesenchymal transition (EMT) of cancer cells. FOXQ1 may exacerbate cancer by activating the oncogenic Wnt/β-catenin signalling pathway. However, the role of FOXQ1 in the Wnt pathway remains to be resolved. Here, we report that FOXQ1 is an activator of Wnt-induced transcription and regulator of β-catenin target gene expression. Upon Wnt pathway activation, FOXQ1 synergises with the β-catenin nuclear complex to boost the expression of major Wnt targets. In parallel, we find that FOXQ1 controls the differential expression of various Wnt target genes in a β-catenin-independent manner. Using RNA sequencing of colorectal cancer cell lines, we show that Wnt signalling and FOXQ1 converge on a transcriptional programme linked to EMT and cell migration. Additionally, we demonstrate that FOXQ1 occupies Wnt-responsive elements in β-catenin target gene promoters and recruits a similar set of co-factors to the β-catenin-associated transcription factor Tcf7l1. Taken together, our results indicate a multifaceted role of FOXQ1 in Wnt/β-catenin signalling, which may drive the metastasis of colorectal cancers.

Clinical Genomics Linköping [Service]

PubMed 36124643

DOI 10.1242/jcs.260082

Crossref 10.1242/jcs.260082

pii: 277173

Publications 8.1.1