FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.

BACKGROUND: The forkhead box transcription factor FOXQ1 has been shown to be upregulated in colorectal cancer (CRC) and metastatic breast cancer and involved in tumor development, epithelial-mesenchymal transition and chemoresistance. Yet, its transcriptional regulation is still unknown. METHODS: FO...

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Main Authors: Jon Christensen, Susanne Bentz, Thierry Sengstag, V Prasad Shastri, Pascale Anderle
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3608605?pdf=render
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author Jon Christensen
Susanne Bentz
Thierry Sengstag
V Prasad Shastri
Pascale Anderle
author_facet Jon Christensen
Susanne Bentz
Thierry Sengstag
V Prasad Shastri
Pascale Anderle
author_sort Jon Christensen
collection DOAJ
description BACKGROUND: The forkhead box transcription factor FOXQ1 has been shown to be upregulated in colorectal cancer (CRC) and metastatic breast cancer and involved in tumor development, epithelial-mesenchymal transition and chemoresistance. Yet, its transcriptional regulation is still unknown. METHODS: FOXQ1 mRNA and protein expression were analysed in a panel of CRC cell lines, and laser micro-dissected human biopsy samples by qRT-PCR, microarray GeneChip® U133 Plus 2.0 and western blots. FOXQ1 regulation was assayed by chromatin immunoprecipitation and luciferase reporter assays. RESULTS: FOXQ1 was robustly induced in CRC compared to other tumors, but had no predictive value with regards to grade, metastasis and survival in CRC. Prototype-based gene coexpression and gene set enrichment analysis showed a significant association between FOXQ1 and the Wnt pathway in tumors and cancer cell lines from different tissues. In vitro experiments confirmed, on a molecular level, FOXQ1 as a direct Wnt target. Analysis of known Wnt targets identified FOXQ1 as the most suitable marker for canonical Wnt activation across a wide panel of cell lines derived from different tissues. CONCLUSIONS: Our data show that FOXQ1 is one of the most over-expressed genes in CRC and a direct target of the canonical Wnt pathway. It is a potential new marker for detection of early CRC and Wnt activation in tumors of different origins.
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spelling doaj.art-583771f745484d618531c03314d75d692022-12-21T18:41:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e6005110.1371/journal.pone.0060051FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.Jon ChristensenSusanne BentzThierry SengstagV Prasad ShastriPascale AnderleBACKGROUND: The forkhead box transcription factor FOXQ1 has been shown to be upregulated in colorectal cancer (CRC) and metastatic breast cancer and involved in tumor development, epithelial-mesenchymal transition and chemoresistance. Yet, its transcriptional regulation is still unknown. METHODS: FOXQ1 mRNA and protein expression were analysed in a panel of CRC cell lines, and laser micro-dissected human biopsy samples by qRT-PCR, microarray GeneChip® U133 Plus 2.0 and western blots. FOXQ1 regulation was assayed by chromatin immunoprecipitation and luciferase reporter assays. RESULTS: FOXQ1 was robustly induced in CRC compared to other tumors, but had no predictive value with regards to grade, metastasis and survival in CRC. Prototype-based gene coexpression and gene set enrichment analysis showed a significant association between FOXQ1 and the Wnt pathway in tumors and cancer cell lines from different tissues. In vitro experiments confirmed, on a molecular level, FOXQ1 as a direct Wnt target. Analysis of known Wnt targets identified FOXQ1 as the most suitable marker for canonical Wnt activation across a wide panel of cell lines derived from different tissues. CONCLUSIONS: Our data show that FOXQ1 is one of the most over-expressed genes in CRC and a direct target of the canonical Wnt pathway. It is a potential new marker for detection of early CRC and Wnt activation in tumors of different origins.http://europepmc.org/articles/PMC3608605?pdf=render
spellingShingle Jon Christensen
Susanne Bentz
Thierry Sengstag
V Prasad Shastri
Pascale Anderle
FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.
PLoS ONE
title FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.
title_full FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.
title_fullStr FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.
title_full_unstemmed FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.
title_short FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.
title_sort foxq1 a novel target of the wnt pathway and a new marker for activation of wnt signaling in solid tumors
url http://europepmc.org/articles/PMC3608605?pdf=render
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