FOXM1

FOXM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3G73
Identifiers
Aliases	FOXM1, FKHL16, FOXM1B, HFH-11, HFH11, HNF-3, INS-1, MPHOSPH2, MPP-2, MPP2, PIG29, TGT3, TRIDENT, forkhead box M1, FOXM1A, FOXM1C
External IDs	OMIM: 602341 MGI: 1347487 HomoloGene: 7318 GeneCards: FOXM1
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12p13.33 Start 2,857,680 bp[1] End 2,877,174 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 F3|6 62.98 cM Start 128,339,930 bp[2] End 128,353,109 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence sperm stromal cell of endometrium rectum secondary oocyte appendix bone marrow cells trabecular bone lymph node skin of abdomen Top expressed in secondary oocyte otic placode yolk sac seminiferous tubule spermatid thymus saccule spermatocyte atrium maxillary prominence More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding DNA-binding transcription factor activity protein binding protein kinase binding RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA-binding transcription repressor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus nucleoplasm Biological process positive regulation of double-strand break repair regulation of Ras protein signal transduction negative regulation of transcription by RNA polymerase II regulation of reactive oxygen species metabolic process transcription by RNA polymerase II transcription, DNA-templated regulation of cell cycle cellular response to DNA damage stimulus regulation of cell population proliferation G2/M transition of mitotic cell cycle regulation of cell growth positive regulation of cell population proliferation negative regulation of stress-activated MAPK cascade negative regulation of transcription, DNA-templated DNA repair positive regulation of transcription by RNA polymerase II DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator regulation of transcription, DNA-templated anatomical structure morphogenesis cell differentiation cell cycle positive regulation of transcription, DNA-templated Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2305 14235 Ensembl ENSG00000111206 ENSMUSG00000001517 UniProt Q08050 O08696 RefSeq (mRNA) NM_001243088 NM_001243089 NM_021953 NM_202002 NM_202003 NM_008021 RefSeq (protein) NP_001230017 NP_001230018 NP_068772 NP_973731 NP_973732 n/a Location (UCSC) Chr 12: 2.86 – 2.88 Mb Chr 6: 128.34 – 128.35 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Forkhead box protein M1 is a protein that in humans is encoded by the FOXM1 gene.^[5][6] The protein encoded by this gene is a member of the FOX family of transcription factors.^[5][7] Its potential as a target for future cancer treatments led to it being designated the 2010 Molecule of the Year.^[8]

Function

FOXM1 is known to play a key role in cell cycle progression where endogenous FOXM1 expression peaks at S and G2/M phases.^[9] FOXM1-null mouse embryos were neonatal lethal as a result of the development of polyploid cardiomyocytes and hepatocytes, highlighting the role of FOXM1 in mitotic division. More recently a study using transgenic/knockout mouse embryonic fibroblasts and human osteosarcoma cells (U2OS) has shown that FOXM1 regulates expression of a large array of G2/M-specific genes, such as Plk1, cyclin B2, Nek2 and CENPF, and plays an important role in maintenance of chromosomal segregation and genomic stability.^[10]

Cancer link

FOXM1 gene is now known as a human proto-oncogene.^[11] Abnormal upregulation of FOXM1 is involved in the oncogenesis of basal cell carcinoma, the most common human cancer worldwide.^[12] FOXM1 upregulation was subsequently found in the majority of solid human cancers including liver,^[13] breast,^[14] lung,^[15] prostate,^[16] cervix of uterus,^[17] colon,^[18] and brain.^[19]

Isoforms

There are three FOXM1 isoforms in humans, A, B and C. Isoform FOXM1A has been shown to be a gene transcriptional repressor whereas the remaining isoforms (B and C) are both transcriptional activators. Hence, it is not surprising that FOXM1B and C isoforms have been found to be upregulated in human cancers.^[9]

Mechanism of oncogenesis

The exact mechanism of FOXM1 in cancer formation remains unknown. It is thought that upregulation of FOXM1 promotes oncogenesis through abnormal impact on its multiple roles in cell cycle and chromosomal/genomic maintenance. Aberrant upregulation of FOXM1 in primary human skin keratinocytes can directly induce genomic instability in the form of loss of heterozygosity (LOH) and copy number aberrations.^[20]

FOXM1 overexpression is involved in early events of carcinogenesis in head and neck squamous cell carcinoma. It has been shown that nicotine exposure directly activates FOXM1 activity in human oral keratinocytes and induced malignant transformation.^[21]

Role in stem cell fate

A recent report by the research group which first found that the over-expression of FOXM1 is associated with human cancer, showed that aberrant upregulation of FOXM1 in adult human epithelial stem cells induces a precancer phenotype in a 3D-organotypic tissue regeneration system – a condition similar to human hyperplasia. The authors showed that excessive expression of FOXM1 exploits the inherent self-renewal proliferation potential of stem cells by interfering with the differentiation pathway, thereby expanding the progenitor cell compartment. It was therefore hypothesized that FOXM1 induces cancer initiation through stem/progenitor cell expansion.^[22]

Role in epigenome regulations

Given the role in progenitor/stem cells expansion,^[22] FOXM1 has been shown to modulate the epigenome. It was found that overexpression of FOXM1 "brain washes" normal cells to adopt cancer-like epigenome.^[23] A number of new epigenetic biomarkers influenced by FOXM1 were identified from the study and these were thought to represent epigenetic signature of early cancer development which has potential for early cancer diagnosis and prognosis.^[23]

Interactions

FOXM1 has been shown to interact with Cdh1.^[24]

See also

• FOX proteins

References

External links

• FOXM1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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