Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''FOXA1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Function
FOXA1 is a member of the
forkhead class of DNA-binding proteins. These
hepatocyte nuclear factors are transcriptional activators for liver-specific transcripts such as
albumin
Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Album ...
and
transthyretin
Transthyretin (TTR or TBPA) is a transport protein in the plasma and cerebrospinal fluid that transports the thyroid hormone thyroxine (T4) and retinol to the liver. This is how transthyretin gained its name: ''transports thyroxine and retinol' ...
, and they also interact with
chromatin
Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important ...
as a
pioneer factor. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver.
Marker in breast cancer
FOXA1 in
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...
is highly correlated with
ERα+,
GATA3+, and
PR+ protein expression as well as
endocrine signaling. FOXA1 acts as a
pioneer factor for ERa in ERα
+ breast cancer, and its expression might identify ERα
+ cancers that undergo rapid reprogramming of ERa signaling that is associated with poor outcomes and treatment resistance. Conversely, in ERα
− breast cancer FOXA1 is highly correlated with low-grade morphology and improved disease free survival. FOXA1 is a downstream target of
GATA3 in the mammary gland.
Expression in ERα
− cancers may identify a subset of tumors that is responsive to other endocrine therapies such as
androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in ...
antagonist treatment.
Role in cancer
Mutations in this gene have been recurrently seen in instances of prostate cancer.
Expression of FOXA1 correlates with two EMT markers, namely Twist1 and E-cadherin in breast cancer.
References
Further reading
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External links
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{{Transcription factors, g3
Forkhead transcription factors