FOXA1

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FOXA1
Identifiers
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000129514

ENSMUSG00000035451

UniProt

P55317

P35582

RefSeq (mRNA)

NM_004496

NM_008259

RefSeq (protein)

NP_004487

NP_032285

Location (UCSC)Chr 14: 37.59 – 37.6 MbChr 12: 57.59 – 57.59 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the FOXA1 gene.[5][6][7]

Function

FOXA1 is a pioneer factor, a transcription factor that directly binds condensed chromatin, facilitating the binding of other transcription factors.[8] In prostate cells, FOXA1 interacts with the androgen receptor (AR) to drive transcription of prostate-specific genes.[8]

FOXA1 is a member of the forkhead class of DNA-binding proteins. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver.[5]

Structure

FOXA1 is a member of the forkhead domain transcription factor family. The forkhead domain is essential for its DNA-binding function, and consists of three

major groove and the wings directly contact the DNA.[9]

Marker in breast cancer

FOXA1 in

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.[10] 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.[11] Expression in ERα− cancers may identify a subset of tumors that is responsive to other endocrine therapies such as androgen receptor antagonist treatment.[12][13]

Role in cancer

FOXA1 is one of the most frequently altered genes in prostate cancer, with mutations in the coding sequence of up to 9% of localized prostate cancer cases, and 13% of metastatic treatment-resistant prostate cancers.[8] Most cancer-associated FOXA1 mutations are missense mutations, changing the amino acid sequence of the fork head domain's DNA-binding sites.[8]

Expression of FOXA1 correlates with two

E-cadherin in breast cancer.[14]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000129514 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035451 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: forkhead box A1".
  6. PMID 8652662
    .
  7. PMID 9119385
    .
  8. ^
    PMID 32946061
    .
  9. PMID 34225008
    .
  10. PMID 22217937
    .
  11. PMID 17129787
    .
  12. PMID 19549328
    .
  13. PMID 19747394
    .
  14. S2CID 91190545
    .

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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