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Forkhead box M1
Identifiers
Symbols FOXM1; FKHL16; FOXM1B; HFH-11; HFH11; HNF-3; INS-1; MPHOSPH2; MPP-2; MPP2; PIG29; TRIDENT
External IDs OMIM602341 MGI1347487 HomoloGene7318 GeneCards: FOXM1 Gene
RNA expression pattern
PBB GE FOXM1 202580 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2305 14235
Ensembl ENSG00000111206 ENSMUSG00000001517
UniProt Q08050 Q6DI64
RefSeq (mRNA) NM_021953 NM_008021
RefSeq (protein) NP_068772 NP_032047
Location (UCSC) Chr 12:
2.84 - 2.86 Mb
Chr 6:
128.33 - 128.35 Mb
PubMed search [1] [2]

Forkhead box protein M1 is a protein that in humans is encoded by the FOXM1 gene.[1][2][2] The protein encoded by this gene is a member of the FOX family of transcription factors.[1][3]

Contents

Function

FOXM1 is known to play a key role in cell cycle progression where endogenous FOXM1 expression peaks at S and G2/M phases.[4] 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.[5]

Cancer link

FOXM1 gene is now known as a human proto-oncogene.[6] Abnormal upregulation of FOXM1 is involved in the oncogenesis of basal cell carcinoma, the most common human cancer worldwide.[7] FOXM1 upregulation was subsequently found in the majority of solid human cancers including liver,[8] breast,[9] lung,[10] prostate,[11] cervix of uterus,[12] colon,[13] pancreas,[14] and brain.[15]

There are three FOXM1 isoforms, 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.[4]

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.

FOXM1 overexpression is involved in early events of carcinogenesis in head and neck squamous cell carcinoma.[16]

See also


Interactions

FOXM1 has been shown to interact with CDH1.[17]

References

  1. ^ a b Ye H, Kelly TF, Samadani U, Lim L, Rubio S, Overdier DG, Roebuck KA, Costa RH (March 1997). "Hepatocyte nuclear factor 3/fork head homolog 11 is expressed in proliferating epithelial and mesenchymal cells of embryonic and adult tissues". Mol Cell Biol 17 (3): 1626–41. PMID 9032290.  
  2. ^ a b Korver W, Roose J, Heinen K, Weghuis DO, de Bruijn D, van Kessel AG, Clevers H (March 1998). "The human TRIDENT/HFH-11/FKHL16 gene: structure, localization, and promoter characterization". Genomics 46 (3): 435–42. doi:10.1006/geno.1997.5065. PMID 9441747.  
  3. ^ "Entrez Gene: FOXM1 forkhead box M1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2305.  
  4. ^ a b Wierstra I, Alves J (December 2007). "FOXM1, a typical proliferation-associated transcription factor". Biol. Chem. 388 (12): 1257–74. doi:10.1515/BC.2007.159. PMID 18020943.  
  5. ^ Laoukili J, Kooistra MR, Brás A, et al. (February 2005). "FoxM1 is required for execution of the mitotic programme and chromosome stability". Nat. Cell Biol. 7 (2): 126–36. doi:10.1038/ncb1217. PMID 15654331.  
  6. ^ Myatt SS, Lam EW (November 2007). "The emerging roles of forkhead box (Fox) proteins in cancer". Nat. Rev. Cancer 7 (11): 847–59. doi:10.1038/nrc2223. PMID 17943136.  
  7. ^ Teh MT, Wong ST, Neill GW, Ghali LR, Philpott MP, Quinn AG (15 August 2002). "FOXM1 is a downstream target of Gli1 in basal cell carcinomas". Cancer Res. 62 (16): 4773–80. PMID 12183437. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12183437.  
  8. ^ Kalinichenko VV, Major ML, Wang X, Petrovic V, Kuechle J, Yoder HM, Dennewitz MB, Shin B, Datta A, Raychaudhuri P, Costa RH (April 2004). "Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor". Genes Dev. 18 (7): 830–50. doi:10.1101/gad.1200704. PMID 15082532.  
  9. ^ Wonsey DR, Follettie MT (June 2005). "Loss of the forkhead transcription factor FoxM1 causes centrosome amplification and mitotic catastrophe". Cancer Res. 65 (12): 5181–9. doi:10.1158/0008-5472.CAN-04-4059. PMID 15958562.  
  10. ^ Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, Major ML, Gusarova GA, Yoder HM, Costa RH, Kalinichenko VV (February 2006). "The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer". Cancer Res. 66 (4): 2153–61. doi:10.1158/0008-5472.CAN-05-3003. PMID 16489016.  
  11. ^ Kalin TV, Wang IC, Ackerson TJ, Major ML, Detrisac CJ, Kalinichenko VV, Lyubimov A, Costa RH (February 2006). "Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice". Cancer Res. 66 (3): 1712–20. doi:10.1158/0008-5472.CAN-05-3138. PMID 16452231.  
  12. ^ Chan D, Yu S, Chiu P, Yao K, Liu V, Cheung A, Ngan H (July 2008). "Over-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis". J. Pathol. 215 (3): 245–52. doi:10.1002/path.2355. PMID 18464245.  
  13. ^ Douard R, Moutereau S, Pernet P, Chimingqi M, Allory Y, Manivet P, Conti M, Vaubourdolle M, Cugnenc PH, Loric S (May 2006). "Sonic Hedgehog-dependent proliferation in a series of patients with colorectal cancer". Surgery 139 (5): 665–70. doi:10.1016/j.surg.2005.10.012. PMID 16701100.  
  14. ^ Wang Z, Banerjee S, Kong D, Li Y, Sarkar FH (September 2007). "Down-regulation of Forkhead Box M1 transcription factor leads to the inhibition of invasion and angiogenesis of pancreatic cancer cells". Cancer Res. 67 (17): 8293–300. doi:10.1158/0008-5472.CAN-07-1265. PMID 17804744.  
  15. ^ Liu M, Dai B, Kang SH, Ban K, Huang FJ, Lang FF, Aldape KD, Xie TX, Pelloski CE, Xie K, Sawaya R, Huang S (April 2006). "FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells". Cancer Res. 66 (7): 3593–602. doi:10.1158/0008-5472.CAN-05-2912. PMID 16585184.  
  16. ^ Gemenetzidis E, Bose A, Riaz AM, Chaplin T, Young BD, Ali M, Sugden D, Thurlow JK, Cheong SC, Teo SH, Wan H, Waseem A, Parkinson EK, Fortune F, Teh MT (2009). "FOXM1 upregulation is an early event in human squamous cell carcinoma and it is enhanced by nicotine during malignant transformation". PLoS ONE 4 (3): e4849. doi:10.1371/journal.pone.0004849. PMID 19287496.  
  17. ^ Laoukili, Jamila; Alvarez-Fernandez Monica, Stahl Marie, Medema René H (Sep. 2008). "FoxM1 is degraded at mitotic exit in a Cdh1-dependent manner". Cell Cycle (United States) 7 (17): 2720–6. PMID 18758239.  

External links

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

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