Biomarker: Yes-associated protein (YAP)

Histology type: endometrioid endometrial carcinoma

Followed up time :

Subgroup 1 name : Low

Subgroup 1 number: 54

Subgroup 2 name: High

Subgroup 2 number: 66

Conclusion: Nuclear YAP expression could be useful as a prognostic indicator or therapeutic target and predict radiation sensitivity in patients with EMCA.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : nuclear expression(score 2/3/4)

Expression elevation: Immunostained slides were evaluated for both nuclear and cytoplasmic glandular staining of YAP by a gynecological pathologist, (H.K.), scoring for intensity using a 5 point (0 to 4) scale.

Funtion description: YAP knockdown by siRNA resulted in a significant decrease in cell proliferation (p<0.05), anchorage-dependent growth and migration/invasion, and a significant increase in the number of cells in G0/G1 phase. Conversely, YAP overexpression promoted cell proliferation. Clonogenic assay demonstrated enhanced radiosensitivity by approximately 36% in YAP inhibited cells.

Funtion Uniprot: Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637, PubMed:30447097). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288). Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization (PubMed:25778702). Plays a key role in controlling cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:18158288). The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction (PubMed:18579750). Suppresses ciliogenesis via acting as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). In conjunction with WWTR1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity).Isoform 2 Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).Isoform 3 Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).

UniProt ID: P46937

UniProt Link: https://www.uniprot.org/uniprotkb/P46937/entry

Biological function from UniProt: #Transcription #Transcription regulation

Molecular function from UniProt:

Tissue specificity from UniProt: Increased expression seen in some liver and prostate cancers. Isoforms lacking the transactivation domain found in striatal neurons of patients with Huntington disease (at protein level).

Subcellular UniProt: #Cytoplasm #Nucleus

Alternative name from UniProt:

Recommended name: Transcriptional coactivator YAP1

Gene name from HGNC: YAP1 (YAP65)

HPA class: Disease related genes Human disease related genes

AlphaFold DB: P46937

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P46937

HPA link: https://www.proteinatlas.org/ENSG00000137693-YAP1

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Cytoplasmic and nuclear expression in most tissues, including smooth muscle.

Single cell type specificity Cell type enhanced (Astrocytes)

Immune cell specificity: Not detected in immune cells

Subcellular summary HPA Located in Nucleoplasm, Nucleoli, Cell Junctions

Cancer prognostic summary HPA Prognostic marker in pancreatic cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000137693-YAP1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000137693-YAP1/pathology/endometrial+cancer

Phenotype ID: 120433

Disease: Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or intellectual disability (COB1)

Note1: The disease is caused by variants affecting the gene represented in this entry

Note2: A number sign (#) is used with this entry because of evidence that ocular coloboma with or without hearing impairment, cleft lip/palate, and/or mental retardation (COB1) is caused by heterozygous mutation in the YAP1 gene (606608) on chromosome 11q22.

OMIM: 606608

OMIM link1: https://www.omim.org/entry/120433

OMIM link2: https://www.omim.org/entry/606608;https://www.omim.org/entry/120433;

Phenotype: Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation

HGNC ID: HGNC:16262

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16262