FOXQ1 (forkhead box Q1)

2014-04-01   Jon Christensen , Pascale Anderle 

Institute for Macromolecular Chemistry, Alber-Ludwigs-University of Freiburg, Freiburg, Germany (JC); Swiss Institute of Bioinformatics, Lausanne, Switzerland (PA)

Identity

HGNC
LOCATION
6p25.3
LOCUSID
ALIAS
HFH1

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).

Proteins

Atlas Image
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.
Atlas Image
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

Entity name
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 name
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 name
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 name
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 name
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 name
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 name
Non-small-cell lung carcinoma
Prognosis
FOXQ1 expression was associated with poor prognosis and EMT (Feng et al., 2012).
Entity name
Ovarian cancer
Oncogenesis
FOXQ1 expression increased ovarian cancer cell proliferation, invasion and induced an EMT phenotype (Gao et al., 2012).

Bibliography

Pubmed IDLast YearTitleAuthors
237230772013Unraveling the role of FOXQ1 in colorectal cancer metastasis.Abba M et al
117476062001Isolation and characterization of the human forkhead gene FOXQ1.Bieller A et al
235558802013FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.Christensen J et al
83322121993Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5.Clark KL et al
227619302012FoxQ1 overexpression influences poor prognosis in non-small cell lung cancer, associates with the phenomenon of EMT.Feng J et al
207179542011The Forkhead factor FoxQ1 influences epithelial differentiation.Feuerborn A et al
106794702000Winged helix proteins.Gajiwala KS et al
232030392012The role of forkhead box Q1 transcription factor in ovarian epithelial carcinomas.Gao M et al
185449312008Impairment of gastric acid secretion and increase of embryonic lethality in Foxq1-deficient mice.Goering W et al
113098492001The winged helix/forkhead transcription factor Foxq1 regulates differentiation of hair in satin mice.Hong HK et al
201451542010FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth.Kaneda H et al
236090352013Increased expression of FOXQ1 is a prognostic marker for patients with gastric cancer.Liang SH et al
157225542005Differences 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 et al
168352202006Evidence that the satin hair mutant gene Foxq1 is among multiple and functionally diverse regulatory targets for Hoxc13 during hair follicle differentiation.Potter CS et al
213461432011FOXQ1 regulates epithelial-mesenchymal transition in human cancers.Qiao Y et al
181719842007Transcriptome profile of human colorectal adenomas.Sabates-Bellver J et al
233832672013FoxQ1 promotes glioma cells proliferation and migration by regulating NRXN3 expression.Sun HT et al
185580922008Transcription factor foxq1 controls mucin gene expression and granule content in mouse stomach surface mucous cells.Verzi MP et al
236233602013The prognostic significance of FOXQ1 oncogene overexpression in human hepatocellular carcinoma.Wang W et al
234894302013R164C mutation in FOXQ1 H3 domain affects formation of the hair medulla.Wu B et al
240059892014Forkhead box Q1 promotes hepatocellular carcinoma metastasis by transactivating ZEB2 and VersicanV1 expression.Xia L et al
212852532011Forkhead transcription factor foxq1 promotes epithelial-mesenchymal transition and breast cancer metastasis.Zhang H et al
234038652013Short hairpin RNA targeting FOXQ1 inhibits invasion and metastasis via the reversal of epithelial-mesenchymal transition in bladder cancer.Zhu Z et al

Other Information

Locus ID:

NCBI: 94234
MIM: 612788
HGNC: 20951
Ensembl: ENSG00000164379

Variants:

dbSNP: 94234
ClinVar: 94234
TCGA: ENSG00000164379
COSMIC: FOXQ1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000164379ENST00000296839Q9C009

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45

References

Pubmed IDYearTitleCitations
212852532011Forkhead transcription factor foxq1 promotes epithelial-mesenchymal transition and breast cancer metastasis.66
201451542010FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth.64
213461432011FOXQ1 regulates epithelial-mesenchymal transition in human cancers.59
240059892014Forkhead box Q1 promotes hepatocellular carcinoma metastasis by transactivating ZEB2 and VersicanV1 expression.50
250989392014MiR-124 suppresses tumor growth and metastasis by targeting Foxq1 in nasopharyngeal carcinoma.46
271195062016MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1.32
195336532009Atrogin-1, MuRF1, and FoXO, as well as phosphorylated GSK-3beta and 4E-BP1 are reduced in skeletal muscle of chronic spinal cord-injured patients.29
252515032015Double-negative feedback loop between microRNA-422a and forkhead box (FOX)G1/Q1/E1 regulates hepatocellular carcinoma tumor growth and metastasis.24
253567532014Involvement of FoxQ1 in NSCLC through regulating EMT and increasing chemosensitivity.22
259551042015FOXQ1 mediates the crosstalk between TGF-β and Wnt signaling pathways in the progression of colorectal cancer.22

Citation

Jon Christensen ; Pascale Anderle

FOXQ1 (forkhead box Q1)

Atlas Genet Cytogenet Oncol Haematol. 2014-04-01

Online version: http://atlasgeneticsoncology.org/gene/45906/foxq1