Modulation of glycosyltransferase ST6Gal-I in gastric cancer-derived organoids disrupts homeostatic epithelial cell turnover Cell Biology

Programmed cell death promotes homeostatic cell turnover in the epithelium but is dysregulated in cancer. The glycosyltransferase ST6Gal-I is known to block homeostatic apoptosis through α2,6-linked sialylation of the death receptor TNFR1 in many cell types. However, its role has not been investigated in gastric epithelial cells or gastric tumorigenesis. We determined that human gastric antral epithelium rarely expressed ST6Gal-I, but the number of ST6Gal-I–expressing epithelial cells increased significantly with advancing premalignancy leading to cancer. The mRNA expression levels of ST6GAL-I and SOX9 in human gastric epithelial cells correlated positively with one another through the premalignancy cascade, indicating that increased epithelial cell expression of ST6Gal-I is associated with premalignant progression. To determine the functional impact of increased ST6Gal-I, we generated human gastric antral organoids from epithelial stem cells and differentiated epithelial monolayers from gastric organoids. Gastric epithelial stem cells strongly expressed ST6Gal-I, suggesting a novel biomarker of stemness. In contrast, organoid-derived epithelial monolayers expressed markedly reduced ST6Gal-I and underwent TNF-induced, caspase-mediated apoptosis, consistent with homeostasis. Conversely, epithelial monolayers generated from gastric cancer stem cells retained high levels of ST6Gal-I and resisted TNF-induced apoptosis, supporting prolonged survival. Protection from TN...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Glycobiology and Extracellular Matrices Source Type: research

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Conclusions: We can conclude that MAD2 is important for GCSCs stemness and its downregulation in MKN45CSCs plays a central role in GC tumorigenesis, likely through CXCR4-SNAI2-MMP1. Thus, its potential use in the clinical setting should be studied as its functions appear to extend beyond mitosis.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
ConclusionIn conclusion, all these data show thatH.  pylori-induced autophagy is implicated in gastric CSC emergence and could represent an interesting therapeutic target.
Source: Gastric Cancer - Category: Gastroenterology Source Type: research
Abstract The tropomyosin-related kinase B (TrkB) receptor is a member of the neurotrophic tyrosine kinase receptors family and, together with the brain-derived neurotrophic factor (BDNF), plays an important role in the development of breast cancer, lung cancer, neuroblastoma, colorectal cancer, leukemia, cervical cancer, gallbladder cancer, gastric cancer, kidney cancer, Ewing's sarcoma, esophageal cancer, and head and neck cancer. Overexpression of these two factors has been associated with increased processes involved in carcinogenesis, such as invasion, migration, epithelial-mesenchymal transition (EMT), angiog...
Source: Cytokine - Category: Molecular Biology Authors: Tags: Cytokine Source Type: research
Conclusions: pMCSCs might be a specific subpopulation that can be sequentially enriched by intraperitoneal transplantation. pMCSCs exhibited a tendency towards partial mesenchymal-epithelial transition, enhancing their invasiveness during homing and the formation of peritoneal tumors. However, these preliminary findings require validation in further experiments. PMID: 32831823 [PubMed - as supplied by publisher]
Source: Gastroenterology Research and Practice - Category: Gastroenterology Tags: Gastroenterol Res Pract Source Type: research
Authors: Gong DY, Chen X, Yang TL, Wang Y, Guo Y, Zeng JH, Chen SZ Abstract Gastric cancer remains the third leading cause of cancer-associated mortality worldwide. The identification of prognostic indicators that are associated with clinical characteristics is urgently required. The aim of the present study was to determine the involvement of epithelial cell transforming 2 (ECT2) in gastric cancer. The results of the present study demonstrated that ECT2 expression was upregulated in human gastric cancer samples. Furthermore, high ECT2 expression was associated with advanced Tumor-Node-Metastasis stage and deeper t...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
The objective is to start treating chronic diseases from the root and not the symptoms of the disease. As we are starting to enroll patients in "senolytics-clinical trials," it will be imperative to assess if senolysis efficiently targets the primary cause of disease or if it works best in combination with other drugs. Additional basic science research is required to address the fundamental role of senescent cells, especially in the established contexts of disease. Notes on Self-Experimentation with Sex Steroid Ablation for Regrowth of the Thymus https://www.fightaging.org/archives/2020/04/notes-on-se...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Cellular metabolism plays important functions in dictating stem cell behaviors, although its role in stomach epithelial homeostasis has not been evaluated in depth. Here, we show that the energy sensor AMP kinase (AMPK) governs gastric epithelial progenitor differentiation. Administering the AMPK activator metformin decreases epithelial progenitor proliferation and increases acid-secreting parietal cells (PCs) in mice and organoids. AMPK activation targets Krüppel-like factor 4 (KLF4), known to govern progenitor proliferation and PC fate choice, and PGC1α, which we show controls PC maturation a...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
Abstract EBV-associated gastric carcinoma (EBVaGC) is accompanied by massive lymphocyte infiltration, but therapy resistance and tumor progression still occur in patients with EBVaGC. Cancer stem cells (CSCs) are reported to possess immunomodulatory ability that allows them to resist immune-mediated rejection for many tumor types. However, whether and how CSCs in EBVaGC exhibit immunosuppression has not yet been elucidated. We isolated CSC-like sphere-forming cells (SFCs) from EBVaGC cell line SNU-719 using the cancer sphere method. We validated their CSC-associated properties in the expression of the epithelial-m...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research
In conclusion, miR-345 plays an inhibitory role in GC metastasis through inhibiting cell migration, EMT, and cancer stem cell phenotype via inactivation of Rac1 signaling by targeting EPS8, which provides the potential therapeutic and predictive value of miR-345 in GC. PMID: 32147678 [PubMed - as supplied by publisher]
Source: Acta Biochimica et Biophysica Sinica - Category: Biochemistry Authors: Tags: Acta Biochim Biophys Sin (Shanghai) Source Type: research
AbstractDigestive system cancers are the most frequent cancers worldwide and often associated with poor prognosis because of their invasive and metastatic characteristics. Recent studies have found that the plasticity of cancer cells can impart cancer stem-like properties via the epithelial –mesenchymal transition (EMT). Cancer stem-like properties such as tumor initiation are integral to the formation of metastasis, which is the main cause of poor prognosis. Numerous markers of cancer stem cells (CSCs) have been identified in many types of cancer. Therefore, CSCs, via their stem cel l-like functions, may play an imp...
Source: Surgery Today - Category: Surgery Source Type: research
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