NKG2D and its ligands, MICA and MICB, are known as the key regulators of NK cells. NK cells are the first reconstituted cells after the allogeneic hematopoietic stem cell transplantation (HSCT); therefore, it is crucial to understand their role in HSCT outcome. In the presented study, we investigated the single amino acid changes across the exons 2-4 of MICA and MICB genes, and point mutations within the NKG2D gene, which defines the type of NKG2D haploblock (HNK/LNK) in the donors (n = 124), as well as in patients with acute myeloid leukemia (n = 78). In our cohort, we found that graft from a donor with at least one MICA allele containing glycine at position 14 (MICA-14Gly) is significantly associated with deterioration of a patient's overall survival (OS) (p < 0.05). We also observed a negative effect of MICB-58 (Lys → Glu) polymorphism on relapse-free survival (RFS), although it was not statistically significant in multivariate analysis (p = 0.069). To our knowledge, this is the first work describing the role of MICA-14 and MICB-58 polymorphisms on HSCT outcome.

• Publikační typ
• časopisecké články MeSH

The molecular machinery of endoplasmic reticulum (ER) integrates various intracellular and extracellular cues to maintain homeostasis in diverse physiological or pathological scenarios. ER stress and the unfolded protein response (UPR) have been found to mediate molecular and biochemical mechanisms that affect cell proliferation, differentiation, and apoptosis. Although a number of reviews on the ER stress response have been published, comprehensive reviews that broadly summarize ER physiology in the context of pluripotency, embryonic development, and tissue homeostasis are lacking. This review complements the current ER literature and provides a summary of the important findings on the role of the ER stress and UPR in embryonic development and pluripotent stem cells.

• MeSH
• buněčná diferenciace * MeSH
• embryonální vývoj * MeSH
• homeostáza MeSH
• lidé MeSH
• pluripotentní kmenové buňky cytologie   metabolismus   MeSH
• stres endoplazmatického retikula * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Ovarian cancer is one of the most common malignancies in women and contributes greatly to cancer-related deaths. Tumor suppressor candidate 3 (TUSC3) is a putative tumor suppressor gene located at chromosomal region 8p22, which is often lost in epithelial cancers. Epigenetic silencing of TUSC3 has been associated with poor prognosis, and hypermethylation of its promoter provides an independent biomarker of overall and disease-free survival in ovarian cancer patients. TUSC3 is localized to the endoplasmic reticulum in an oligosaccharyl tranferase complex responsible for the N-glycosylation of proteins. However, the precise molecular role of TUSC3 in ovarian cancer remains unclear. In this study, we establish TUSC3 as a novel ovarian cancer tumor suppressor using a xenograft mouse model and demonstrate that loss of TUSC3 alters the molecular response to endoplasmic reticulum stress and induces hallmarks of the epithelial-to-mesenchymal transition in ovarian cancer cells. In summary, we have confirmed the tumor-suppressive function of TUSC3 and identified the possible mechanism driving TUSC3-deficient ovarian cancer cells toward a malignant phenotype.

• MeSH
• epitelo-mezenchymální tranzice genetika   MeSH
• heterografty MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• myši inbrední NOD MeSH
• myši SCID MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádorové supresorové proteiny genetika   MeSH
• nádory vaječníků genetika   MeSH
• stres endoplazmatického retikula genetika   MeSH
• tumor supresorové geny fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Prostate cancer is the most prevalent cancer in males in developed countries. Tumor suppressor candidate 3 (TUSC3) has been identified as a putative tumor suppressor gene in prostate cancer, though its function has not been characterized. TUSC3 shares homologies with the yeast oligosaccharyltransferase (OST) complex subunit Ost3p, suggesting a role in protein glycosylation. We provide evidence that TUSC3 is part of the OST complex and affects N-linked glycosylation in mammalian cells. Loss of TUSC3 expression in DU145 and PC3 prostate cancer cell lines leads to increased proliferation, migration and invasion as well as accelerated xenograft growth in a PTEN negative background. TUSC3 downregulation also affects endoplasmic reticulum (ER) structure and stress response, which results in increased Akt signaling. Together, our findings provide first mechanistic insight in TUSC3 function in prostate carcinogenesis in general and N-glycosylation in particular.

• MeSH
• aktivace enzymů MeSH
• endoplazmatické retikulum metabolismus   ultrastruktura   MeSH
• genový knockdown MeSH
• glykosylace MeSH
• hexosyltransferasy chemie   metabolismus   MeSH
• interakční proteinové domény a motivy MeSH
• lidé MeSH
• membránové proteiny chemie   nedostatek   genetika   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• nádorové buněčné linie MeSH
• nádorové supresorové proteiny nedostatek   genetika   metabolismus   MeSH
• nádory prostaty genetika   metabolismus   patologie   MeSH
• pohyb buněk MeSH
• proliferace buněk MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• signální transdukce MeSH
• stres endoplazmatického retikula * genetika   MeSH
• tumor burden MeSH
• vazba proteinů MeSH
• viabilita buněk genetika   MeSH
• xenogenní modely - testy antitumorózní aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH