FOXM1

Forkhead box M1, also known as FOXM1, is a human gene.cite journal | author = Korver W, Roose J, Heinen K, Weghuis DO, de Bruijn D, van Kessel AG, Clevers H | title = The human TRIDENT/HFH-11/FKHL16 gene: structure, localization, and promoter characterization | journal = Genomics | volume = 46 | issue = 3 | pages = 435–42 | year = 1997 | month = December | pmid = 9441747 | doi = 10.1006/geno.1997.5065 | url = ] The protein encoded by this gene is a member of the FOX family of transcription factors.cite web | title = Entrez Gene: FOXM1 forkhead box M1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2305| accessdate = ] cite journal | author = Ye H, Kelly TF, Samadani U, Lim L, Rubio S, Overdier DG, Roebuck KA, Costa RH | title = Hepatocyte nuclear factor 3/fork head homolog 11 is expressed in proliferating epithelial and mesenchymal cells of embryonic and adult tissues | journal = Mol. Cell. Biol. | volume = 17 | issue = 3 | pages = 1626–41 | year = 1997 | month = March | pmid = 9032290 | pmc = 231888 | url = http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=9032290 | issn = ]

Function

FOXM1 is known to play a key role in cell cycle progression where endogenous FOXM1 expression peaks at S and G2/M phases.cite journal | author = Wierstra I, Alves J | title = FOXM1, a typical proliferation-associated transcription factor | journal = Biol. Chem. | volume = 388 | issue = 12 | pages = 1257–74 | year = 2007 | month = December | pmid = 18020943 | doi = 10.1515/BC.2007.159 | url = | issn = ] 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. [cite journal |author=Laoukili J, Kooistra MR, Brás A, "et al" |title=FoxM1 is required for execution of the mitotic programme and chromosome stability |journal=Nat. Cell Biol. |volume=7 |issue=2 |pages=126–36 |year=2005 |month=February |pmid=15654331 |doi=10.1038/ncb1217 |url=]

Cancer link

FOXM1 gene is now known as a human proto-oncogene.cite journal | author = Myatt SS, Lam EW | title = The emerging roles of forkhead box (Fox) proteins in cancer | journal = Nat. Rev. Cancer | volume = 7 | issue = 11 | pages = 847–59 | year = 2007 | month = November | pmid = 17943136 | doi = 10.1038/nrc2223 | url = | issn = ] Abnormal upregulation of FOXM1 is involved in the oncogenesis of basal cell carcinoma, the most common human cancer worldwide.cite journal | author = Teh MT, Wong ST, Neill GW, Ghali LR, Philpott MP, Quinn AG | title = FOXM1 is a downstream target of Gli1 in basal cell carcinomas | journal = Cancer Res. | volume = 62 | issue = 16 | pages = 4773–80 | year = 2002 | month = August | pmid = 12183437 | url = http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12183437 | issn = ] FOXM1 upregulation was subsequently found in the majority of solid human cancers including liver,cite journal | author = Kalinichenko VV, Major ML, Wang X, Petrovic V, Kuechle J, Yoder HM, Dennewitz MB, Shin B, Datta A, Raychaudhuri P, Costa RH | title = Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor | journal = Genes Dev. | volume = 18 | issue = 7 | pages = 830–50 | year = 2004 | month = April | pmid = 15082532 | pmc = 387422 | doi = 10.1101/gad.1200704 | url = ] breast,cite journal | author = Wonsey DR, Follettie MT | title = Loss of the forkhead transcription factor FoxM1 causes centrosome amplification and mitotic catastrophe | journal = Cancer Res. | volume = 65 | issue = 12 | pages = 5181–9 | year = 2005 | month = June | pmid = 15958562 | doi = 10.1158/0008-5472.CAN-04-4059 | url = ] lung,cite journal | author = Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, Major ML, Gusarova GA, Yoder HM, Costa RH, Kalinichenko VV | title = The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer | journal = Cancer Res. | volume = 66 | issue = 4 | pages = 2153–61 | year = 2006 | month = February | pmid = 16489016 | doi = 10.1158/0008-5472.CAN-05-3003 | url = ] prostate,cite journal | author = Kalin TV, Wang IC, Ackerson TJ, Major ML, Detrisac CJ, Kalinichenko VV, Lyubimov A, Costa RH | title = Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice | journal = Cancer Res. | volume = 66 | issue = 3 | pages = 1712–20 | year = 2006 | month = February | pmid = 16452231 | pmc = 1363687 | doi = 10.1158/0008-5472.CAN-05-3138 | url = ] cervix of uterus,cite journal | author = Chan D, Yu S, Chiu P, Yao K, Liu V, Cheung A, Ngan H | title = Over-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis | journal = J. Pathol. | volume = 215 | issue = 3 | pages = 245–52 | year = 2008 | month = July | pmid = 18464245 | doi = 10.1002/path.2355 | url = ] colon,cite journal | author = Douard R, Moutereau S, Pernet P, Chimingqi M, Allory Y, Manivet P, Conti M, Vaubourdolle M, Cugnenc PH, Loric S | title = Sonic Hedgehog-dependent proliferation in a series of patients with colorectal cancer | journal = Surgery | volume = 139 | issue = 5 | pages = 665–70 | year = 2006 | month = May | pmid = 16701100 | doi = 10.1016/j.surg.2005.10.012 | url = ] pancreas,cite journal | author = Wang Z, Banerjee S, Kong D, Li Y, Sarkar FH | title = Down-regulation of Forkhead Box M1 transcription factor leads to the inhibition of invasion and angiogenesis of pancreatic cancer cells | journal = Cancer Res. | volume = 67 | issue = 17 | pages = 8293–300 | year = 2007 | month = September | pmid = 17804744 | doi = 10.1158/0008-5472.CAN-07-1265 | url = ] and brain.cite journal | author = Liu M, Dai B, Kang SH, Ban K, Huang FJ, Lang FF, Aldape KD, Xie TX, Pelloski CE, Xie K, Sawaya R, Huang S | title = FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells | journal = Cancer Res. | volume = 66 | issue = 7 | pages = 3593–602 | year = 2006 | month = April | pmid = 16585184 | doi = 10.1158/0008-5472.CAN-05-2912 | url = ] 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.cite journal | author = Wierstra I, Alves J | title = FOXM1, a typical proliferation-associated transcription factor | journal = Biol. Chem. | volume = 388 | issue = 12 | pages = 1257–74 | year = 2007 | month = December | pmid = 18020943 | doi = 10.1515/BC.2007.159 | url = ]

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.

ee also

* FOX proteins

References

External links

*

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