title: DKK3 attenuates the cytotoxic effect of natural killer cells on CD133+gastric cancer cells.
abstract: Cancer stem cell (CSCs) has started a new era in cancer research. CD133 is a widely used marker for identification of CSCs. More and more studies showed that NK cells preferentially target cancer stem-like cells. However, the deeper mechanism of the susceptibility of cancer stem cells to NK cells remains unclear. In this study, we isolated CD133 positive population of a gastric cancer cell line, BGC823 cells, and cultured with NK cells. We found that CD133 could efficiently active NK cells in an NKG2D-dependent manner. DKK3 has been demonstrated as a suppressor in many cancers. Interestingly, we found that DKK3 suppressed CD133-induced activation in NK cells by inhibiting Erk pathway and immunological synapse (IS) formation. NK cells-based CSCs immunotherapy may be a novel approach for cancer therapy.
authors.affiliation: Department of Cell Biology, College of Basic Medical Science, Liaoning Medical University, Jinzhou, Liaoning, P.R. China.
authors.forename: Pu
authors.identifier: 0000-0002-5206-0270
authors.initials: P
authors.lastname: Xia
authors.affiliation: Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, Liaoning, P.R. China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Xu
mesh_terms: D000071916:AC133 Antigen / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000556:secondary; D017209:Apoptosis; D016022:Case-Control Studies; D049109:Cell Proliferation; D018925:Chemokines; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D013270:Stomach / Q000276:immunology / Q000473:pathology; D013274:Stomach Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; C000606023:PROM1 protein, human
keywords: CD133; CSCs; DKK3; NK cells; gastric cancer