Journal
JOURNAL OF CELL SCIENCE
Volume 135, Issue 19, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.260082
Keywords
Colorectal cancer; Forkhead box; Gene expression; Proteomics; Wnt signalling
Categories
Funding
- Knut och AliceWallenbergs Stiftelse
- Vetenskapsradet [2020-01084]
- Cancerfonden [0737 Pj 01, CAN 2018/542]
- Linkopings Universitet
- Vinnova [2020-01084] Funding Source: Vinnova
- Swedish Research Council [2020-01084] Funding Source: Swedish Research Council
Ask authors/readers for more resources
The forkhead box transcription factor FOXQ1 plays a crucial role in the pathogenesis of colorectal cancers by promoting tumour metastasis and activating the Wnt/beta-catenin signalling pathway. FOXQ1 enhances Wnt-induced transcription and regulates the expression of beta-catenin target genes. It also controls the expression of various Wnt target genes independently of beta-catenin. Furthermore, FOXQ1 is involved in a transcriptional program linked to EMT and cell migration, and interacts with similar co-factors as the beta-catenin-associated transcription factor Tcf711.
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/beta-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 beta-catenin target gene expression. Upon Wnt pathway activation, FOXQ1 synergises with the beta-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 beta-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 beta-catenin target gene promoters and recruits a similar set of co-factors to the beta-catenin-associated transcription factor Tcf711. Taken together, our results indicate a multifaceted role of FOXQ1 in Wnt/beta-catenin signalling, which may drive the metastasis of colorectal cancers.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available