SNAIL proteiinien osuudesta EMT :ssä . CRUMBS proteiinit

• Published: 04 February 2008
•  DOIhttps://doi.org/10.1038/onc.2008.9

The transcription factor snail represses Crumbs3 expression and disrupts apico-basal polarity complexes E L Whiteman,

• 
  

Oncogene volume 27, pages 3875–3879 (2008)Cite this articleAbstract

In epithelial cells, the tight junction divides the plasma membrane into distinct apical and basolateral domains. Polarization is essential for epithelial cell function, and apico-basal cell polarity is lost during the epithelial to mesenchymal transition (EMT), a program of events characterized not only by loss of cell polarity, but also by enhanced cell motility and increased cell invasion. Among several apically localized protein complexes, the Crumbs and Par protein complexes have pivotal roles in control of epithelial polarity and apical membrane formation. Here, we demonstrate that the Snail transcriptional repressor antagonizes expression of the Crumbs polarity complex. We show that Snail abolishes localization of the Crumbs and Par complexes to the tight junction, decreases Crumbs complex protein levels and suppresses Crumbs3 transcription. Evidence that Snail acts directly to antagonize Crumbs3 promoter activity is presented. Strikingly, we note that reexpression of exogenous Crumbs3 in Snail-expressing Madin–Darby Canine Kidney cells partially restores cell–cell junctions. Moreover, we find that the EMT inducer transforming growth factor-β elicits transcriptional repression of Crumbs3 and results in a measurable loss of Crumbs3 protein. Our findings provide new insights into the links between the transcriptional repression function of Snail and its role in antagonizing key apico-basal polarity factors during EMT.

 CRUMB1, RP12 (1q31.3)  (Mutaatio: Retinitis pigmentosa 12CRUMBS family membre 1photoreceptor morphogennesis associated  protein crumbs homolog , RP12. https://www.genecards.org/cgi-bin/carddisp.pl?gene=CRB1&keywords=CRUMBS1

CRB2  vaikuttaa retinaan ja aivokortexiin. Muistiin   " Muisti"  blogiin. https://www.genecards.org/cgi-bin/carddisp.pl?gene=CRB2

https://www.genecards.org/cgi-bin/carddisp.pl?gene=CRB2&keywords=CRB2

CRUMB3, CRB3  (19p13.3)   (Tästä löytyy yhteyttä TGFb1 tien kautta SNAI1 ja SMAD7 expression  säätelyyn.

https://www.genecards.org/cgi-bin/carddisp.pl?gene=CRB3&keywords=CRUMB

• This gene encodes a member of the Crumbs family of proteins. This gene is widely expressed in epithelial tissues where the encoded protein isoforms play various roles such as the control of cytokinesis and ciliogenesis or the formation of tight junctions. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

   CRB3 (Crumbs Cell Polarity Complex Component 3) is a Protein Coding gene. Diseases associated with CRB3 include Retinitis Pigmentosa 12 and Charcot-Marie-Tooth Disease, Demyelinating, Type 4F. Among its related pathways are Cell junction organization and Infectious disease. Gene Ontology (GO) annotations related to this gene include protein domain specific binding and SH3 domain binding. An important paralog of this gene is CRB2.

CRB3 (Crumbs Cell Polarity Complex Component 3) is a Protein Coding gene. Diseases associated with CRB3 include Retinitis Pigmentosa 12 and Charcot-Marie-Tooth Disease, Demyelinating, Type 4F. Among its related pathways are Cell junction organization and Infectious disease. Gene Ontology (GO) annotations related to this gene incl ude protein domain specific binding and SH3 domain binding. An important paralog of this gene is CRB2.

Molecular function for CRB3 Gene according to UniProtKB/Swiss-Prot

FunctionInvolved in the establishment of cell polarity in mammalian epithelial cells (PubMed:12771187, 14718572).Regulates the morphogenesis of tight junctions (PubMed:12771187, 14718572).

 

Involved in promoting phosphorylation and cytoplasmic retention of transcriptional coactivators YAP1 and WWTR1/TAZ which leads to suppression of TGFB1-dependent transcription of target genes such as CCN2/CTGF, SERPINE1/PAI1, SNAI1/SNAIL1 and SMAD7 (By similarity). CRUM3_HUMAN,Q9BUF7

HAKU PubMed CRM3  and Cancer13.3. 2024 ,  Vastauksia 126. Haen jonkin uusimmista.

https://pubmed.ncbi.nlm.nih.gov/?term=crb3+cancer

 Crumbs protein homolog 3 (CRB3) expression is associated with oestrogen and progesterone receptor positivity in breast cancer.

Li P, Zhou C, Yan Y, Li J, Liu J, Zhang Y, Liu P. Clin Exp Pharmacol Physiol. 2019 Sep;46(9):837-844. doi: 10.1111/1440-1681.13104. Epub 2019 Jun 10. PMID: 31087799 Free PMC article.The crumbs protein homolog 3 (CRB3) regulates the tight junction to help maintain epithelial polarity. Altered CRB3 expression was associated with carcinogenesis of epithelial cells. This study detected CRB3 expression in 192 cases of breast cancer tissues and in the Molecular Taxonomy of Breast Cancer International Consortium (Metabric) and The Cancer Genome Atlas (TCGA) datasets for association with triple negative breast cancer (TNBC) phenotypes. The in vitro experiments confirm the ex vivo data. The data showed that levels of both CRB3 mRNA and protein were associated with TNBC phenotypes, ie, 41.1% (39/95) of ER+ breast cancer was CRB3-positive, whereas 26.9% (25/93) ER- tumour was CRB3-positive (P = 0.046). Moreover, 47.6% (30/63) of PR+ breast cancer was CRB3-positive vs 28.4% (33/116) PR- tumours positive for CRB3 (P = 0.013). In addition, 40.1% (27/66) of ER+/PR+ tumour was CRB3-positive, but only 22.4% (19/85) of TNBC showed CRB3 expression (P = 0.048). Indeed, levels of CRB3 mRNA were higher in non-TNBC than TNBC in both Metabric (P = 3.682e-10) and TCGA datasets (P = 2.501e-07). The in vitro data showed that CRB3 expression was higher in luminal (MCF7 and T47D) than in HER2 (MDA-MB-453 and SK-BR-3) and basal (MDA-MB-231 and BT-549) breast cancer cell lines. More interestingly, ERα regulated expression of CRB3 protein in MCF7 and BT-549 cells and ERα expression was associated with CRB3 expression in breast cancer tissues specimens. This study demonstrated that ERα could be a novel regulator for CRB3 expression in breast cancer. Keywords: CRB3; Her2/neu; breast cancer; oestrogen receptor; progesterone receptor. 

• CRB3 navigates Rab11 trafficking vesicles to promote gammaTuRC assembly during ciliogenesis.

Wang B, Liang Z, Tan T, Zhang M, Jiang Y, Shang Y, Gao X, Song S, Wang R, Chen H, Liu J, Li J, Ren Y, Liu P. Elife. 2023 Sep 22;12:RP86689. doi: 10.7554/eLife.86689. PMID: 37737843 Free PMC article.

Dysfunction of the primary cilium can lead to ciliopathies and cancer. The formation and organization of the primary cilium are highly associated with cell polarity proteins, such as the apical polarity protein CRB3. However, the molecular mechanisms by which CRB …