Identifiers
BMI1 polycomb ring finger oncogene
"B lymphoma Mo-MLV insertion region 1 homolog (mouse)", PCGF4, "polycomb group ring finger 4"
HUGO:BMI1 HGNC:1066 ENTREZ:648 UNIPROT:P35226
Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / SENESCENCE
HMC:SUSTAINING_PROLIFERATIVE_SIGNALLING
Cell Cycle DNA Repair / G1_S_CHECKPOINT
References
PMID:22796940
The silencing of E-cadherin expression by hypermethylation is a common event in cancer.
DNMTs target cytosine residues in CpG dinucleotides for methylation and have been identified in the repression of E-cadherin in normal and pathological contexts
such as colorectal cancer, gastric cancer and hepatocellular carcinomas.
Multiple signaling pathways involved in EMT and tumorigenesis activate DNMTs, e.g., ras43 and TGF-b.
DNMTs bind several histone remodeling enzymes, such as Sirtuin and G9a.
However, SNAI1 has been shown to be linked to DNMT1, notably in association with G9a and Suv39H1.
Cooperation between Polycomb proteins and EMT-inducing transcription factors.
The polycomb proteins are part of repressor complexes that inhibit gene expression through chromatin remodeling.
The polycomb repressive complex 2 (PRC2) recruits PRC1 after chromatin methylation at H3K27 through enhancer of EZH2, a histone H3 lysine-27-specific methyltransferase.
Both, PRC1 and PRC2 have been shown to interact with SNAI1 and TWIST1 to promote EMT.
SNAI1 is stabilized through its interaction with the PRC1 component BMI1 and interacts with EZH2 and Suz12 to repress CDH1 expression.
Interestingly, EZH2 also participates in TGFb1 signaling, a potent inducer of EMT.
BMI-1 can also interact with TWIST to induce EMT.
Repression of E-cadherin by SNAI1/TWIST1 involves the recruitment of histone remodeling proteins to the promoter, where SNAI1 interacts with histone deacetylase HDAC1 and HDAC2.
The intricate interactions of EMT-inducing transcription factors and chromatin remodeling complexes PRC1 and PRC2 may offer novel approaches to control EMT and thus cell adhesion in cancer cells via a plethora of new drug, such as HDACs and DNMT inhibitors.
PMID:17936558, PMID:21678481, PMID:21685941, PMID:21383063
References
em_emtc_emtc_re1204( EMT Senescence ):
PMID:20818389
Physical interaction between BMI1 and TWIST1
E-Cadherin repression by cooperative BMI1 and TWIST1
p16INK4A repression by cooperative BMI1 and TWIST1
References
em_emtc_emtc_re1198( EMT Senescence ):
PMID:19935649
Protein expression of Bmi1, Sox2, p63 was reduced after ZEB1 knockdown.
ZEB1 knockdown not only resulted in reduced invasion and metastasis, but also in reduced tumorigenicity.
ZEB1 is also necessary for the self-renewing capacity.
ZEB1 is crucial for drug resistance in pancreatic cancer cells. This supports data showing that EMT activators (Twist and Snail) confer anti-apoptotic properties
References
ce_re399( Cell Cycle DNA Repair ):
Repression of p15INK4b expression by Myc through association with Miz-1:
PMID:9308237, PMID:11283613
Repression of pINK expression by BMI1:
PMID:17936558