Biomarker: Snail

Histology type: endometrial carcinoma

Country: Japanese

Region: Osaka

Followed up time :

Subgroup 1 name : negative

Subgroup 1 number: 292

Subgroup 2 name: positive

Subgroup 2 number: 60

Conclusion: The current study is the first report to demonstrate that the EMT status, as represented by both reduced E-cadherin expression and nuclear Snail expression, was identified to be an independent predictive factor of patient survival in endometrial cancer.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : EMT (reduced E-cadherin and nuclear expression of Snail )

Expression elevation: E-cadherin expression was scored as: 0 (no stain), 1+ (low intensity immunoreactivity in more than 10% of tumor cells), 2+ (medium intensity immunoreactivity of more than 10% of tumor cells), 3+ (high intensity immunoreactivity of more than 10% of tumor cells). These data were summarized into two groups; preserved E-cadherin (3+) and reduced E-cadherin (0, 1+, 2+). The Snail and Slug expressions were evaluated as positive only when nuclear staining was detectable: 0 (no stain), 1+ (immunoreactivity of more than 1% of tumor cells), 2+ (immunoreactivity of more than 2–5% of tumor cells), 3+ (immunoreactivity of more than 5% of tumor cells), then divided into two groups, negative (0), and positive (1+, 2+, 3+). Scoring was performed three times per slide for three distinct fields, and the three scores were averaged.

Statictics: cutoff<50;cutoff>50

Cohort age: 68;286

Subgroup 1 age: 64;230

Subgroup 2 age: 4;56

Funtion Uniprot: Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration. Binds to 3 E-boxes of the E-cadherin/CDH1 gene promoter and to the promoters of CLDN7 and KRT8 and, in association with histone demethylase KDM1A which it recruits to the promoters, causes a decrease in dimethylated H3K4 levels and represses transcription (PubMed:20389281, PubMed:20562920). The N-terminal SNAG domain competes with histone H3 for the same binding site on the histone demethylase complex formed by KDM1A and RCOR1, and thereby inhibits demethylation of histone H3 at 'Lys-4' (in vitro) (PubMed:20389281, PubMed:21300290, PubMed:23721412). During EMT, involved with LOXL2 in negatively regulating pericentromeric heterochromatin transcription (By similarity). SNAI1 recruits LOXL2 to pericentromeric regions to oxidize histone H3 and repress transcription which leads to release of heterochromatin component CBX5/HP1A, enabling chromatin reorganization and acquisition of mesenchymal traits (By similarity). Associates with EGR1 and SP1 to mediate tetradecanoyl phorbol acetate (TPA)-induced up-regulation of CDKN2B, possibly by binding to the CDKN2B promoter region 5'-TCACA-3. In addition, may also activate the CDKN2B promoter by itself

UniProt ID: O95863

UniProt Link: https://www.uniprot.org/uniprotkb/O95863/entry

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed in a variety of tissues with the highest expression in kidney. Expressed in mesenchymal and epithelial cell lines.

Subcellular UniProt: #Cytoplasm #Nucleus

Alternative name from UniProt:

Caution: The interaction with mouse KPNA2 may prevent SNAI1 nuclear import.

Recommended name: Zinc finger protein SNAI1

Gene name from HGNC: SNAI1 (SLUGH2, SNA, SNAH, SNAIL, SNAIL1)

HPA class: Transcription factors

AlphaFold DB: O95863

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/O95863

Induction: Induced by TPA maximally by 2.5-fold at 4 hours, in HepG2 cells (at protein level).

HPA link: https://www.proteinatlas.org/ENSG00000124216-SNAI1

Tissue specificity RNA from HPA: Tissue enhanced (adipose tissue)

Tissue expression from HPA: Ubiquitous nuclear expression.

Single cell type specificity Cell type enhanced (Adipocytes, Extravillous trophoblasts, Endothelial cells)

Immune cell specificity: Immune cell enhanced (plasmacytoid DC)

Subcellular summary HPA Located in Nucleoplasm

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable), thyroid cancer (unfavorable), lung cancer (unfavorable) and colorectal cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000124216-SNAI1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000124216-SNAI1/pathology/endometrial+cancer

Expression figure legend: Survival curves generated by using the Kaplan-Meier method in 354 endometrial cancer patients.

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566047/figure/F2/?report=objectonly

OMIM: 604238

OMIM link2: https://www.omim.org/entry/604238

HGNC ID: HGNC:11128

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11128