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FOXQ1 (forkhead box Q1)

Written2014-04Jon Christensen, Pascale Anderle
Institute for Macromolecular Chemistry, Alber-Ludwigs-University of Freiburg, Freiburg, Germany (JC); Swiss Institute of Bioinformatics, Lausanne, Switzerland (PA)

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)HFH1
Other alias
HGNC (Hugo) FOXQ1
LocusID (NCBI) 94234
Atlas_Id 45906
Location 6p25.3  [Link to chromosome band 6p25]
Location_base_pair Starts at 1312440 and ends at 1314758 bp from pter ( according to hg19-Feb_2009)  [Mapping FOXQ1.png]

DNA/RNA

Description The FOXQ1 gene is 2338 base pairs in length and is intronless.
Transcription In mouse Foxq1 has been reported to be regulated by Hoxa1 (Martinez-Ceballos et al., 2005), Hoxc13 (Potter et al., 2006) and Tgfβ (Zhang et al., 2011). In human FOXQ1 has been shown to be a target of the Wnt pathway (Christensen et al., 2013; Xia et al., 2014).

Protein

 
  Figure 1. Structure of the winged helix domain. α-helices are shown as red cylinders (H1, H2 and H3), β-strands as blue arrows and W1 and W2 denote the wings (Clark et al., 1993; Gajiwala and Burley, 2000).
Description The forkhead box Q1 gene codes for a 403 amino acid long protein with a size of 41.5 kDa. FOXQ1 is a member of the Forkhead box (Fox) superfamily. The family members share a conserved DNA-binding domain named forkhead box or winged helix domain. The domain consists of three a-helices, three β-sheets and two loops termed wings.
 
  Figure 2. Graphical illustration of the FOXQ1 amino acid sequence and domains. (I) Acid and serine-rich domain. (WH) winged helix domain. (II) Serin-rich domain. (III) Proline-rich domain. (IV) Functional conserved domain (Hong et al., 2001; Wu et al., 2013).
Expression Predominantly in the stomach, trachea, bladder and salivary gland (Bieller et al., 2001).
Function In mice Foxq1 is involved in hair follicle differentiation (Hong et al., 2001; Potter et al., 2006). A mutation in the Foxq1 gene is responsible for an impaired differentiation of the hair shaft in the satin mice (Hong et al., 2001). In the digestive system Foxq1 has been shown to regulate acid secretion and expression of Muc5ac (Goering et al., 2008; Verzi et al., 2008).
Homology According to NCBI the following genes have been suggested to be putative homologues: FOXQ1 (H. sapiens), Foxq1 (M. musculus), Foxq1 (R. norvegicus), Foxq1a (D. rerio) and Foxq1b (D. rerio). Conserved domains from CDD found in protein sequences by rpsblast searching was FH (cl00061).

Mutations

Note Mutations in the Foxq1 gene is responsible for the hair follicle defects seen in the satin mouse mutant. Three mutations have been described leading to similar phenotypes of the animals. Foxq1sa has a 67 bp deletion from 686-752 and a base pair change CA-AT at position 766-767. Foxq1sa-el has a point mutation a position 383 changing T to G thus replacing isoleucine with serin at position 128 in the protein. Foxq1sa-J has C to T mutation in position 490 changing the amino acide arginine to cysteine at position 164 in the protein (Hong et al., 2001; Wu et al., 2013).

Implicated in

Note
  
Entity Bladder cancer
Oncogenesis FOXQ1 was overexpressed in bladder cancer samples. Depletion of FOXQ1 expression in bladder cancer cell lines reduced invasiveness and EMT markers (Zhu et al., 2013).
  
  
Entity Breast cancer
Prognosis FOXQ1 expression in breast cancer patients is associated with poor survival, high grade, metastatic status and basal-like phenotype (Qiao et al., 2011).
Oncogenesis FOXQ1 overexpression was observed in invasive breast cancer cell lines compared to non-invasive. FOXQ1 expression increases breast cancer cell proliferation, migration and invasion in vitro and metastasis in vivo (Zhang et al., 2011). FOXQ1 promotes an EMT phenotype through transcriptional regulation of CDH1 (Qiao et al., 2011; Zhang et al., 2011).
  
  
Entity Colorectal cancer
Oncogenesis Several studies have shown FOXQ1 to be overexpressed in colorectal tumor samples compared to healthy colonocytes (Bieller et al., 2001; Sabates-Bellver et al., 2007; Kaneda et al., 2010; Christensen et al., 2013). The increased expression of FOXQ1 could be due to a hyperactive Wnt pathway in these tumors. Wnt activity directly correlates with FOXQ1 expression in colorectal cancer cell lines and β-catenin can bind to the promoter of FOXQ1 and increase transcription (Christensen et al., 2013). FOXQ1 expression can induce an EMT phenotype (Qiao et al., 2011; Abba et al., 2013). FOXQ1 does not increase growth but seems to protect from apoptosis (Kaneda et al., 2010; Qiao et al., 2011; Abba et al., 2013). The anti-apoptotic effect was mediated through FOXQ1 regulation of p21 (Kaneda et al., 2010).
  
  
Entity Gastric cancer
Prognosis The expression of FOXQ1 was a prognostic factor for overall survival and correlated with tumor size, grade and tumor-node metastasis stage (Liang et al., 2013).
Oncogenesis FOXQ1 increases migration and proliferation by downregulating NRXN3.
  
  
Entity Glioma
Disease Tumors that arise from the glial cells, the most common site is the brain.
Oncogenesis FOXQ1 increased migration and proliferation by downregulating NRXN3 (Sun et al., 2013).
  
  
Entity Hepatocarcinoma
Cytogenetics FOXQ1 correlated with overall worse survival and higher recurrence (Wang et al., 2013; Xia et al., 2014).
Oncogenesis In hepatocarcinoma FOXQ1 directly activated the EMT transcription factor ZEB2. This led to an EMT phenotype and increased lung metastasis. FOXQ1 and ZEB2 expression correlated positively in hepatocarcinoma samples but inversely with CDH1. FOXQ1 induced metastasis through regulation of VersicanV1, which promoted tumor-associated-macrophages attraction. Also, similarly to colorectal cancer expression of FOXQ1 was regulated by the Wnt pathway in hepatocarcinoma (Xia et al., 2014).
  
  
Entity Non-small-cell lung carcinoma
Prognosis FOXQ1 expression was associated with poor prognosis and EMT (Feng et al., 2012).
  
  
Entity Ovarian cancer
Oncogenesis FOXQ1 expression increased ovarian cancer cell proliferation, invasion and induced an EMT phenotype (Gao et al., 2012).
  

Bibliography

Unraveling the role of FOXQ1 in colorectal cancer metastasis.
Abba M, Patil N, Rasheed K, Nelson LD, Mudduluru G, Leupold JH, Allgayer H.
Mol Cancer Res. 2013 Sep;11(9):1017-28. doi: 10.1158/1541-7786.MCR-13-0024. Epub 2013 May 30.
PMID 23723077
 
Isolation and characterization of the human forkhead gene FOXQ1.
Bieller A, Pasche B, Frank S, Glaser B, Kunz J, Witt K, Zoll B.
DNA Cell Biol. 2001 Sep;20(9):555-61.
PMID 11747606
 
FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.
Christensen J, Bentz S, Sengstag T, Shastri VP, Anderle P.
PLoS One. 2013;8(3):e60051. doi: 10.1371/journal.pone.0060051. Epub 2013 Mar 26.
PMID 23555880
 
Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5.
Clark KL, Halay ED, Lai E, Burley SK.
Nature. 1993 Jul 29;364(6436):412-20.
PMID 8332212
 
FoxQ1 overexpression influences poor prognosis in non-small cell lung cancer, associates with the phenomenon of EMT.
Feng J, Zhang X, Zhu H, Wang X, Ni S, Huang J.
PLoS One. 2012;7(6):e39937. doi: 10.1371/journal.pone.0039937. Epub 2012 Jun 28.
PMID 22761930
 
The Forkhead factor FoxQ1 influences epithelial differentiation.
Feuerborn A, Srivastava PK, Kuffer S, Grandy WA, Sijmonsma TP, Gretz N, Brors B, Grone HJ.
J Cell Physiol. 2011 Mar;226(3):710-9. doi: 10.1002/jcp.22385.
PMID 20717954
 
Winged helix proteins.
Gajiwala KS, Burley SK.
Curr Opin Struct Biol. 2000 Feb;10(1):110-6. (REVIEW)
PMID 10679470
 
The role of forkhead box q1 transcription factor in ovarian epithelial carcinomas.
Gao M, Shih IeM, Wang TL.
Int J Mol Sci. 2012 Oct 26;13(11):13881-93. doi: 10.3390/ijms131113881.
PMID 23203039
 
Impairment of gastric acid secretion and increase of embryonic lethality in Foxq1-deficient mice.
Goering W, Adham IM, Pasche B, Manner J, Ochs M, Engel W, Zoll B.
Cytogenet Genome Res. 2008;121(2):88-95. doi: 10.1159/000125833. Epub 2008 Jun 9.
PMID 18544931
 
The winged helix/forkhead transcription factor Foxq1 regulates differentiation of hair in satin mice.
Hong HK, Noveroske JK, Headon DJ, Liu T, Sy MS, Justice MJ, Chakravarti A.
Genesis. 2001 Apr;29(4):163-71.
PMID 11309849
 
FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth.
Kaneda H, Arao T, Tanaka K, Tamura D, Aomatsu K, Kudo K, Sakai K, De Velasco MA, Matsumoto K, Fujita Y, Yamada Y, Tsurutani J, Okamoto I, Nakagawa K, Nishio K.
Cancer Res. 2010 Mar 1;70(5):2053-63. doi: 10.1158/0008-5472.CAN-09-2161. Epub 2010 Feb 9.
PMID 20145154
 
Increased expression of FOXQ1 is a prognostic marker for patients with gastric cancer.
Liang SH, Yan XZ, Wang BL, Jin HF, Yao LP, Li YN, Chen M, Nie YZ, Wang X, Guo XG, Wu KC, Ding J, Fan DM.
Tumour Biol. 2013 Oct;34(5):2605-9. doi: 10.1007/s13277-013-0808-x. Epub 2013 Apr 23.
PMID 23609035
 
Differences in gene expression between wild type and Hoxa1 knockout embryonic stem cells after retinoic acid treatment or leukemia inhibitory factor (LIF) removal.
Martinez-Ceballos E, Chambon P, Gudas LJ.
J Biol Chem. 2005 Apr 22;280(16):16484-98. Epub 2005 Feb 18.
PMID 15722554
 
Evidence that the satin hair mutant gene Foxq1 is among multiple and functionally diverse regulatory targets for Hoxc13 during hair follicle differentiation.
Potter CS, Peterson RL, Barth JL, Pruett ND, Jacobs DF, Kern MJ, Argraves WS, Sundberg JP, Awgulewitsch A.
J Biol Chem. 2006 Sep 29;281(39):29245-55. Epub 2006 Jul 10.
PMID 16835220
 
FOXQ1 regulates epithelial-mesenchymal transition in human cancers.
Qiao Y, Jiang X, Lee ST, Karuturi RK, Hooi SC, Yu Q.
Cancer Res. 2011 Apr 15;71(8):3076-86. doi: 10.1158/0008-5472.CAN-10-2787. Epub 2011 Feb 23.
PMID 21346143
 
Transcriptome profile of human colorectal adenomas.
Sabates-Bellver J, Van der Flier LG, de Palo M, Cattaneo E, Maake C, Rehrauer H, Laczko E, Kurowski MA, Bujnicki JM, Menigatti M, Luz J, Ranalli TV, Gomes V, Pastorelli A, Faggiani R, Anti M, Jiricny J, Clevers H, Marra G.
Mol Cancer Res. 2007 Dec;5(12):1263-75. doi: 10.1158/1541-7786.MCR-07-0267.
PMID 18171984
 
FoxQ1 promotes glioma cells proliferation and migration by regulating NRXN3 expression.
Sun HT, Cheng SX, Tu Y, Li XH, Zhang S.
PLoS One. 2013;8(1):e55693. doi: 10.1371/journal.pone.0055693. Epub 2013 Jan 30.
PMID 23383267
 
Transcription factor foxq1 controls mucin gene expression and granule content in mouse stomach surface mucous cells.
Verzi MP, Khan AH, Ito S, Shivdasani RA.
Gastroenterology. 2008 Aug;135(2):591-600. doi: 10.1053/j.gastro.2008.04.019. Epub 2008 Apr 22.
PMID 18558092
 
The prognostic significance of FOXQ1 oncogene overexpression in human hepatocellular carcinoma.
Wang W, He S, Ji J, Huang J, Zhang S, Zhang Y.
Pathol Res Pract. 2013 Jun;209(6):353-8. doi: 10.1016/j.prp.2013.03.005. Epub 2013 Mar 25.
PMID 23623360
 
R164C mutation in FOXQ1 H3 domain affects formation of the hair medulla.
Wu B, Herbert Pratt C, Potter CS, Silva KA, Kennedy V, Sundberg JP.
Exp Dermatol. 2013 Mar;22(3):234-6. doi: 10.1111/exd.12106.
PMID 23489430
 
Forkhead box Q1 promotes hepatocellular carcinoma metastasis by transactivating ZEB2 and VersicanV1 expression.
Xia L, Huang W, Tian D, Zhang L, Qi X, Chen Z, Shang X, Nie Y, Wu K.
Hepatology. 2014 Mar;59(3):958-73. doi: 10.1002/hep.26735. Epub 2014 Feb 6.
PMID 24005989
 
Forkhead transcription factor foxq1 promotes epithelial-mesenchymal transition and breast cancer metastasis.
Zhang H, Meng F, Liu G, Zhang B, Zhu J, Wu F, Ethier SP, Miller F, Wu G.
Cancer Res. 2011 Feb 15;71(4):1292-301. doi: 10.1158/0008-5472.CAN-10-2825. Epub 2011 Feb 1.
PMID 21285253
 
Short hairpin RNA targeting FOXQ1 inhibits invasion and metastasis via the reversal of epithelial-mesenchymal transition in bladder cancer.
Zhu Z, Zhu Z, Pang Z, Xing Y, Wan F, Lan D, Wang H.
Int J Oncol. 2013 Apr;42(4):1271-8. doi: 10.3892/ijo.2013.1807. Epub 2013 Feb 5.
PMID 23403865
 

Citation

This paper should be referenced as such :
J Christensen, P Anderle
FOXQ1 (forkhead box Q1)
Atlas Genet Cytogenet Oncol Haematol. 2015;19(1):11-14.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/FOXQ1ID45906ch6p25.html


External links

Nomenclature
HGNC (Hugo)FOXQ1   20951
Cards
AtlasFOXQ1ID45906ch6p25
Entrez_Gene (NCBI)FOXQ1  94234  forkhead box Q1
AliasesHFH1
GeneCards (Weizmann)FOXQ1
Ensembl hg19 (Hinxton)ENSG00000164379 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000164379 [Gene_View]  chr6:1312440-1314758 [Contig_View]  FOXQ1 [Vega]
ICGC DataPortalENSG00000164379
TCGA cBioPortalFOXQ1
AceView (NCBI)FOXQ1
Genatlas (Paris)FOXQ1
WikiGenes94234
SOURCE (Princeton)FOXQ1
Genetics Home Reference (NIH)FOXQ1
Genomic and cartography
GoldenPath hg38 (UCSC)FOXQ1  -     chr6:1312440-1314758 +  6p25.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)FOXQ1  -     6p25.3   [Description]    (hg19-Feb_2009)
EnsemblFOXQ1 - 6p25.3 [CytoView hg19]  FOXQ1 - 6p25.3 [CytoView hg38]
Mapping of homologs : NCBIFOXQ1 [Mapview hg19]  FOXQ1 [Mapview hg38]
OMIM612788   
Gene and transcription
Genbank (Entrez)BC053850 BM980542 BU566731
RefSeq transcript (Entrez)NM_033260
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)FOXQ1
Cluster EST : UnigeneHs.591352 [ NCBI ]
CGAP (NCI)Hs.591352
Alternative Splicing GalleryENSG00000164379
Gene ExpressionFOXQ1 [ NCBI-GEO ]   FOXQ1 [ EBI - ARRAY_EXPRESS ]   FOXQ1 [ SEEK ]   FOXQ1 [ MEM ]
Gene Expression Viewer (FireBrowse)FOXQ1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)94234
GTEX Portal (Tissue expression)FOXQ1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9C009   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9C009  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9C009
Splice isoforms : SwissVarQ9C009
PhosPhoSitePlusQ9C009
Domaine pattern : Prosite (Expaxy)FORK_HEAD_1 (PS00657)    FORK_HEAD_2 (PS00658)    FORK_HEAD_3 (PS50039)   
Domains : Interpro (EBI)Fork_head_dom    TF_fork_head_CS_1    TF_fork_head_CS_2    WHTH_DNA-bd_dom   
Domain families : Pfam (Sanger)Forkhead (PF00250)   
Domain families : Pfam (NCBI)pfam00250   
Domain families : Smart (EMBL)FH (SM00339)  
Conserved Domain (NCBI)FOXQ1
DMDM Disease mutations94234
Blocks (Seattle)FOXQ1
SuperfamilyQ9C009
Human Protein AtlasENSG00000164379
Peptide AtlasQ9C009
HPRD17015
IPIIPI00018738   
Protein Interaction databases
DIP (DOE-UCLA)Q9C009
IntAct (EBI)Q9C009
FunCoupENSG00000164379
BioGRIDFOXQ1
STRING (EMBL)FOXQ1
ZODIACFOXQ1
Ontologies - Pathways
QuickGOQ9C009
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II transcription factor activity, sequence-specific DNA binding  transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding  nucleus  transcription, DNA-templated  hair follicle morphogenesis  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II transcription factor activity, sequence-specific DNA binding  transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding  nucleus  transcription, DNA-templated  hair follicle morphogenesis  
NDEx NetworkFOXQ1
Atlas of Cancer Signalling NetworkFOXQ1
Wikipedia pathwaysFOXQ1
Orthology - Evolution
OrthoDB94234
GeneTree (enSembl)ENSG00000164379
Phylogenetic Trees/Animal Genes : TreeFamFOXQ1
HOVERGENQ9C009
HOGENOMQ9C009
Homologs : HomoloGeneFOXQ1
Homology/Alignments : Family Browser (UCSC)FOXQ1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerFOXQ1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)FOXQ1
dbVarFOXQ1
ClinVarFOXQ1
1000_GenomesFOXQ1 
Exome Variant ServerFOXQ1
ExAC (Exome Aggregation Consortium)FOXQ1 (select the gene name)
Genetic variants : HAPMAP94234
Genomic Variants (DGV)FOXQ1 [DGVbeta]
DECIPHERFOXQ1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisFOXQ1 
Mutations
ICGC Data PortalFOXQ1 
TCGA Data PortalFOXQ1 
Broad Tumor PortalFOXQ1
OASIS PortalFOXQ1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICFOXQ1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDFOXQ1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch FOXQ1
DgiDB (Drug Gene Interaction Database)FOXQ1
DoCM (Curated mutations)FOXQ1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)FOXQ1 (select a term)
intoGenFOXQ1
NCG5 (London)FOXQ1
Cancer3DFOXQ1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM612788   
Orphanet
MedgenFOXQ1
Genetic Testing Registry FOXQ1
NextProtQ9C009 [Medical]
TSGene94234
GENETestsFOXQ1
Target ValidationFOXQ1
Huge Navigator FOXQ1 [HugePedia]
snp3D : Map Gene to Disease94234
BioCentury BCIQFOXQ1
ClinGenFOXQ1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD94234
Chemical/Pharm GKB GenePA134924898
Clinical trialFOXQ1
Miscellaneous
canSAR (ICR)FOXQ1 (select the gene name)
Probes
Litterature
PubMed42 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineFOXQ1
EVEXFOXQ1
GoPubMedFOXQ1
iHOPFOXQ1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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