Biomarker: CD117

Histology type: endometrial carcinoma

Country: Japan

Region: Ishikawa

Followed up time :

Subgroup 1 name : Low

Subgroup 1 number: 85

Subgroup 2 name: High

Subgroup 2 number: 9

Conclusion: Targeting of the SCF/CD117 axis by imatinib sensitized endometrial cancer cells to cisplatin, proposing a novel therapeutic strategy for this tumor type.

Sample type : tissue

Sample method: immunohistochemistry,RT-PCR,ELISA

Expression pattern : expression(negative, weak (up to 1% of cells stained), moderate (1–10%) or strong (>10%).)

Expression elevation: CD117 expression was assessed semi-quantitatively by two independent investigators as follows: negative, weak (up to 1% of cells stained), moderate (1–10%) or strong (>10%). Immunohistochemically CD117-positive GIST tissue was used as positive control.

Statictics: cutoff<60;cutoff>60

Cohort age: 54;40

Subgroup 1 age: 50;35

Subgroup 2 age: 4;5

Funtion description: In vitro assay confirmed that stem cell factor (SCF), a ligand of CD117, was produced specifically in CD117(+) cells of endometrial cancer, and the colony-forming activity were abrogated by adding anti-SCF antibody, indicating an SCF-dependent growth property. Imatinib was confirmed to selectively target CD117(+) cells in vitro, and synergistically enhanced the anti-tumor effect of low dose cisplatin in vivo, which showed only modest effects when used as a single use.

Funtion Uniprot: Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.

UniProt ID: P10721

UniProt Link: https://www.uniprot.org/uniprotkb/P10721/entry

Molecular function from UniProt:

Tissue specificity from UniProt: Isoform 3 In testis, detected in spermatogonia in the basal layer and in interstitial Leydig cells but not in Sertoli cells or spermatocytes inside the seminiferous tubules (at protein level) (PubMed:20601678). Expression is maintained in ejaculated spermatozoa (at protein level) (PubMed:20601678).

Subcellular UniProt: #Cell membrane #Cytoplasm #Membrane

Alternative name from UniProt:

Miscellaneous: Numerous proteins are phosphorylated in response to KIT signaling, but it is not evident to determine which are directly phosphorylated by KIT under in vivo conditions.

Catalytic activity: ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]

Recommended name: Mast/stem cell growth factor receptor Kit

Gene name from HGNC: KIT (C-Kit, CD117, PBT, SCFR)

CD antigen name: CD117

HPA class: Human disease related genes

AlphaFold DB: P10721

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P10721

Induction: Up-regulated by cis-retinoic acid in neuroblastoma cell lines.

HPA link: https://www.proteinatlas.org/ENSG00000157404-KIT

Tissue specificity RNA from HPA: Tissue enhanced (breast)

Tissue expression from HPA: Selective cytoplasmic and membranous expression in a few cell types including subset of cells in breast, melanocytes in skin, basket cells in cerebellum and subsets of peripheral immune cells.

Single cell type specificity Cell type enhanced (granulocytes, Melanocytes, Inhibitory neurons, Ionocytes, Breast glandular cells)

Immune cell specificity: Group enriched (basophil, NK-cell, eosinophil)

Subcellular summary HPA Located in Plasma membrane (Single cell variability)

Cancer prognostic summary HPA Prognostic marker in renal cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000157404-KIT/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000157404-KIT/pathology/endometrial+cancer

Phenotype ID: 172800;606764;273300;601626;154800;154800;

Disease: Piebald trait (PBT);Gastrointestinal stromal tumor (GIST);Testicular germ cell tumor (TGCT);Leukemia, acute myelogenous (AML);Mastocytosis, cutaneous (MASTC);Mastocytosis, systemic (MASTSYS);

Note1: The disease is caused by variants affecting the gene represented in this entry;The gene represented in this entry is involved in disease pathogenesis;The gene represented in this entry may be involved in disease pathogenesis;The gene represented in this entry is involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of KIT are detected in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the kinase domain can result in a constitutively activated kinase;The disease is caused by variants affecting the gene represented in this entry;The disease is caused by variants affecting the gene represented in this entry;

OMIM: 164920

OMIM link1: https://www.omim.org/entry/172800;https://www.omim.org/entry/606764;https://www.omim.org/entry/273300;https://www.omim.org/entry/601626;https://www.omim.org/entry/154800;https://www.omim.org/entry/154800;

OMIM link2: https://www.omim.org/entry/164920

HGNC ID: HGNC:6342

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6342