title: FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.
abstract: 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.
authors.affiliation: Institute of Macro Molecular Chemistry, Albert-Ludwigs-University of Freiburg, Freiburg, Germany. jon.christensen@makro.uni-freiburg.de
authors.forename: Jon
authors.initials: J
authors.lastname: Christensen
authors.forename: Susanne
authors.initials: S
authors.lastname: Bentz
authors.forename: Thierry
authors.initials: T
authors.lastname: Sengstag
authors.forename: V Prasad
authors.initials: VP
authors.lastname: Shastri
authors.forename: Pascale
authors.initials: P
authors.lastname: Anderle
mesh_terms: D015153:Blotting, Western; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D060888:Real-Time Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*
chemical_list: C484579:FOXQ1 protein, human; D051858:Forkhead Transcription Factors
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