Forkhead box protein C2 (FOXC2) also known as forkhead-related protein FKHL14 (FKHL14), transcription factor FKH-14, or
mesenchyme
Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood, or bone. The interactions between mesenchyme and epithelium help to form nearly ever ...
fork head protein 1 (MFH1) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''FOXC2''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
FOXC2 is a member of the
fork head box (FOX) family of
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
s.
Structure and function
The protein is 501 amino acids in length. The gene has no
introns
An intron is any Nucleic acid sequence, nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of ...
; the single
exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...
is approximately 1.5kb in size.
FOX transcription factors are expressed during development and are associated with a number of cellular and developmental
differentiation processes. FOXC2 is required during early development of the kidneys, including differentiation of
podocytes and maturation of the
glomerular basement membrane. It is also involved in the early development of the heart.
An increased expression of FOXC2 in adipocytes can increase the amount of brown adipose tissue leading to lower weight and an increased sensitivity to insulin.
Role in disease
Absence of FOXC2 has been shown to lead to the failure of lymphatic valves to form and problems with lymphatic remodelling. A number of mutations in the FOXC2 gene have been associated with
Lymphedema–distichiasis syndrome,
It has also been suggested that there may be a link between polymorphisms in FOXC2 and varicose veins.
FOXC2 is also involved in
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
metastases
Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
. In particular, expression of FOXC2 is induced when
epithelial cells undergo an
epithelial-mesenchymal transition (EMT) and become
mesenchymal looking cells. EMT can be induced by a number of genes including
Snail
A snail is a shelled gastropod. The name is most often applied to land snails, terrestrial molluscs, terrestrial pulmonate gastropod molluscs. However, the common name ''snail'' is also used for most of the members of the molluscan class Gas ...
,
Twist,
Goosecoid, and
TGF-beta 1.
Overexpression of FOXC2 has been noted in subtypes of breast cancer which are highly metastatic.
Suppression of FOXC2 expression using
shRNA in a highly metastatic
breast cancer
Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
model blocks their metastatic ability.
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Lymphedema-Distichiasis Syndrome
{{DEFAULTSORT:Foxc2
Forkhead transcription factors