M.Cassandri
ZEB1 on C2H2- sinkkisormiproteiini ja transkriptiofaktori ja osallistuu tuumorin invaasioon ja metaboliaan. Se on EMT:n mestarisäätelijä. Sitä itseään säätelee usea signaalijärjestelmä kuten Wnt, TGF-beeta, NFkB, HIF ja miRNA:t. Sen onkogeeninen rooli on E-cadheriini- proteiinin tukahduttaminen, onhan E-Cad tärkein solu-solu-adheesiomolekyyli.
ZEB1 pääsee vaikuttamaan E-Cadheriiniin tekemällä interaktion useiden kromatiinia muokkaavien tekijäiden kanssa, kuten CtBP ja Swi/SNF-kompleksi.
Toisaalta ZEB1 aktivoi suoraan niiden geenien promoottoreita, jotka osallistuvat EMT-ohjelmaan. ZEB1 tekee interaktion joko SMAD- proteiinien tai p300/CAF kanssa ja aktivoi TGFbeetan kohdegeenin CDH2 (N-Cadheriinin, joka on mesenkymaalinen neuronaalinen cadheriini ja olennainen tuumorin progressiolle).
ZEB1- yli-ilmenemä useissa syöpälinjoissa ( havaittu haima-, keuhko-, maksasyövässä, osteosarkoomassa, rintasyövässä, paksusuolisyövässä) indusoi EMT:tä ja edistää solujen invaasiota. Tieto vuodelta 2017) .
ZEB1 (10p11.22) https://www.ncbi.nlm.nih.gov/gene/6935
BZP; TCF8; AREB6; FECD6; NIL2A; PPCD3; ZFHEP; ZFHX1A; DELTAEF1. This gene encodes a zinc finger transcription factor. The encoded protein likely plays a role in transcriptional repression of interleukin 2. Mutations in this gene have been associated with posterior polymorphous corneal dystrophy-3 and late-onset Fuchs endothelial corneal dystrophy. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2010]
Preferred Names:
zinc finger E-box-binding homeobox 1,
Names:
delta-crystallin enhancer binding factor 1,
negative regulator of IL2,
posterior polymorphous corneal dystrophy 3,
transcription factor 8 (represses interleukin 2 expression.
Tästä ZEB1-geenistä on erikseen toinen otsikko ja lisäartikkeleista maininta.
Tässä kirjoitan artikkelin mainitsemista tekijöistä, joita on EMT prosessissa.
EMT = Epithelial Mesenchymal Transition
E-Cadherin , https://www.ncbi.nlm.nih.gov/gene/999
CDH1, cadherin 1, (16q22) Calcium dependent adhesion protein (epithelial), Cell-CAM 120/80. uvomodulin.
Preferred Names: cadherin-1
Names:
CAM 120/80
E-cadherin 1
cadherin 1, E-cadherin (epithelial)
cadherin 1, type 1, E-cadherin (epithelial)
calcium-dependent adhesion protein, epithelial
cell-CAM 120/80
epididymis secretory sperm binding protein
epithelial cadherin
uvomorulin
N-Cadherin,https://www.ncbi.nlm.nih.gov/gene/1000
CDH2. cadherin 2, (18q12.1), Calcium dependent adhesion protein (neuronal).
Preferred Names, cadherin-2
Names: N-cadherin 1
cadherin 2, type 1, N-cadherin (neuronal)
calcium-dependent adhesion protein, neuronal
neural cadherin
Näistä on joitakin omia otsikoita tässä blogissakin: Olen katsonut netistä signaaliteiden kuvauksia opetusvideoista.
Wnt
TGF-beta
SMAD
NF-kB
HIF
miRNA
CtBP
CTBP1,(4p16.3) C-terminal binding protein 1, brefeldin. https://www.ncbi.nlm.nih.gov/gene/1487
BARS; HADDTS
This gene encodes a protein that binds to the C-terminus of adenovirus E1A proteins. This phosphoprotein is a transcriptional repressor and may play a role during cellular proliferation. This protein and the product of a second closely related gene, CTBP2, can dimerize. Both proteins can also interact with a polycomb group protein complex which participates in regulation of gene expression during development. Alternative splicing of transcripts from this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008] Expression Ubiquitous expression in spleen (RPKM 9.3), prostate (RPKM 7.1) and 25 other tissues See more
Preferred Names:C-terminal-binding protein 1
Names: brefeldin A-ribosylated substrate
Names: brefeldin A-ribosylated substrate
CTBP2, (10q26.13), C-terminal binding protein 2 , ribeye ; 2 isoforms. https://www.ncbi.nlm.nih.gov/gene/1488 This gene produces alternative transcripts encoding two distinct proteins. One protein is a transcriptional repressor, while the other isoform is a major component of specialized synapses known as synaptic ribbons. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. A portion of the 3' untranslated region was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2014] Expression Ubiquitous expression in thyroid (RPKM 13.6), endometrium (RPKM 9.4) and 24 other tissues See more
Preferred Names: C-terminal-binding protein 2
Names: ribeye Transcript Variant: This variant (2) represents the longest transcript and encodes the longer isoform (2). This protein localizes to synaptic ribbons, synapses used for fast tonic neurotransmitter release in a subset of specialized neurons.
´
Swi/SNF complex, https://www.ncbi.nlm.nih.gov/pubmed/28262751
Genes encoding subunits of SWI/SNF (BAF) chromatin remodelling complexes are collectively altered in over 20% of human
malignancies, but the mechanisms by which these complexes alter
chromatin to modulate transcription and cell fate are poorly understood.
Utilizing mouse embryonic fibroblast and cancer cell line models, here
we show via ChIP-seq and biochemical assays that SWI/SNF
complexes are preferentially targeted to distal lineage specific
enhancers and interact with p300 to modulate histone H3 lysine 27
acetylation. We identify a greater requirement for SWI/SNF
at typical enhancers than at most super-enhancers and at enhancers in
untranscribed regions than in transcribed regions. Our data further
demonstrate that SWI/SNF-dependent
distal enhancers are essential for controlling expression of genes
linked to developmental processes. Our findings thus establish SWI/SNF complexes as regulators of the enhancer landscape and provide insight into the roles of SWI/SNF in cellular fate control.
ZEB1- SIRT feedback
https://www.ncbi.nlm.nih.gov/pubmed/30304565
J Cell Biochem. 2019 Mar;120(3):3727-3735. doi: 10.1002/jcb.27653. Epub 2018 Oct 10.SIRT1-ZEB1-positive feedback promotes epithelial-mesenchymal transition process and metastasis of Abstract. Osteosarcoma is the most common malignant bone cancer that mainly affects children and young adults. Recently, the NAD+ -dependent deacetylase, sirtuin
1 (SIRT1), has been reported to play a key role in the development of
malignant tumors. The study aimed to investigate the role of SIRT1 in
osteosarcoma and explore its underlying oncogenic mechanisms. The
prognostic value of SIRT1 in osteosarcoma was assessed through detection
of SIRT1 expression based on osteosarcoma biopsy tissue. Then, to
further investigate the effect of SIRT1 in osteosarcoma, osteosarcoma
cells were treated with small interfering RNA SIRT1 and overexpressed
SIRT1 to detect the cell migration, invasion, and epithelial-mesenchymal
transition (EMT). The levels of SIRT1 expression were significantly
higher in osteosarcoma tissues than those in adjacent normal tissues,
and the SIRT1 protein level may be coupled with metastatic and poor
prognosis risk in patients with osteosarcoma. Moreover, SIRT1 silencing
inhibited the migration as well as invasion ability of osteosarcoma
cells in vitro, and SIRT1 upregulation reversed those effects. Finally,
we found that SIRT1-ZEB1-positive
feedback enhanced the EMT process and metastasis of osteosarcoma.
Altogether, the results of the current study revealed that high levels
of SIRT1 might be a biomarker for a high metastatic rate in patients
with osteosarcoma, which suggested that inhibition of SIRT1 might
be promising for the therapeutics of osteosarcoma.
© 2018 Wiley Periodicals, Inc.
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