Citation

  • Authors: Pizzolato G. et al.
  • Year: 2022
  • Journal: J Cell Sci 135 jcs260082
  • Applications: in vitro / DNA / jetOPTIMUS
  • Cell types:
    1. Name: HCT 116
      Description: Human colon carcinoma cells
      Known as: HCT116
    2. Name: HEK-293T
      Description: Human embryonic kidney Fibroblast
      Known as: HEK293T, 293T

Method

HCT116 and 293T cells were seeded into 96-well plates at a density of 5x103 cells/well and transfected with 50 ng plasmids/well using jetOPTIMUS transfection reagents (Polyplus Transfection, Illkirch, France). Briefly, N-terminal TurboID-FOXQ1 and TurboID plasmids were transiently transfected into 293T cells using jetOPTIMUS (Polyplus Transfection, Illkirch, France). After 21 hours of transfection, cells were treated with 500 µM biotin, and incubated for 3 hours at 37ºC, 5% CO2

Abstract

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/-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 b-catenin target gene expression. Upon Wnt pathway activation, FOXQ1 synergises with the b-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 b-catenin-independent manner. Using RNA sequencing of colorectal cancer cell lines, we show that Wnt signalling and FOXQ1 converge on a transcriptional program linked to EMT and cell migration. Additionally, we demonstrate that FOXQ1 occupies Wnt-responsive elements in b-catenin target gene promoters and recruits a similar set of co-factors as the b-catenin-associated transcription factor Tcf7l1. Taken together, our results indicate a multifaceted role of FOXQ1 in Wnt/b-catenin signalling, which may drive the metastasis of colorectal cancers.

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