FOXQ1 (forkhead box Q1)

2014-04-01 Jon Christensen , Pascale Anderle Affiliation

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

Identity

HGNC

FOXQ1

LOCATION

6p25.3

LOCUSID

94234

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

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. Foxq1^sa has a 67 bp deletion from 686-752 and a base pair change CA-AT at position 766-767. Foxq1^sa-el has a point mutation a position 383 changing T to G thus replacing isoleucine with serin at position 128 in the protein. Foxq1^sa-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 ID	Last Year	Title	Authors

Other Information

Locus ID:

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

Variants:

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

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000164379	ENST00000296839	Q9C009

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

References

Pubmed ID	Year	Title	Citations
21285253	2011	Forkhead transcription factor foxq1 promotes epithelial-mesenchymal transition and breast cancer metastasis.	66
20145154	2010	FOXQ1 is overexpressed in colorectal cancer and enhances tumorigenicity and tumor growth.	64
21346143	2011	FOXQ1 regulates epithelial-mesenchymal transition in human cancers.	59
24005989	2014	Forkhead box Q1 promotes hepatocellular carcinoma metastasis by transactivating ZEB2 and VersicanV1 expression.	50
25098939	2014	MiR-124 suppresses tumor growth and metastasis by targeting Foxq1 in nasopharyngeal carcinoma.	46
27119506	2016	MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1.	32
19533653	2009	Atrogin-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
25251503	2015	Double-negative feedback loop between microRNA-422a and forkhead box (FOX)G1/Q1/E1 regulates hepatocellular carcinoma tumor growth and metastasis.	24
25356753	2014	Involvement of FoxQ1 in NSCLC through regulating EMT and increasing chemosensitivity.	22
25955104	2015	FOXQ1 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/cancer-prone-explorer/humanGenome