Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA229460 | ENA |
REPOSITORIES: ENA
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Project description:Previously, we have identified the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) gene as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that GALNT3 is strongly overexpressed in both LMP and HG serous EOC tumors, thus suggesting that epigenetic mechanisms might be implicated in GALNT3 overexpression in serous epithelial ovarian cancer (EOC). Moreover, GALNT3 expression significantly correlated with shorter progression-free survival (PFS) periods in serous EOC patients with advanced disease. Knockdown of the GALNT3 expression in EOC cells led to sharp decrease of cell proliferation and induced S-phase cell cycle arrest. Additionally, GALNT3 suppression significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon GALNT3 suppression, while some tumor suppressor genes were induced. Moreover, GALNT3 downregulation was associated with reduced MUC1 protein expression in EOC cells, probably related to destabilization of the MUC1 protein due to lack of GALNT3 glycosylation activity.Taken together, our data are indicative for a strong oncogenic potential of the GALNT3 gene in advanced EOC and identify this transferase as a novel EOC biomarker and putative EOC therapeutic target. Our findings also suggest that GALNT3 overexpression might contribute to ovarian etiology through aberrant mucin O-glycosylation. To better understand the molecular mechanisms of GALNT3 gene action in ovarian cancer cells, we employed the Agilent Whole Human Genome microarrays, containing ~ 44,000 genes to identify global gene expression changes upon GALNT3 suppression in A2780s cells. We compared the gene expression of the previously selected clone shRNA- GALNT3-knockdown clones 1 & 2 (sh-cl1 & sh-cl2) against the corresponding control (ctrl) clone. The microarray experiments were performed in duplicates, as four hybridizations were carried out for the GALNT3-suppressing cell clones against the corresponding control, using a fluorescent dye reversal (dye-swap) technique.
2014-05-22 | E-GEOD-52602 | biostudies-arrayexpress
Project description:Previously, we have identified the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) gene as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that GALNT3 is strongly overexpressed in both LMP and HG serous EOC tumors, thus suggesting that epigenetic mechanisms might be implicated in GALNT3 overexpression in serous epithelial ovarian cancer (EOC). Moreover, GALNT3 expression significantly correlated with shorter progression-free survival (PFS) periods in serous EOC patients with advanced disease. Knockdown of the GALNT3 expression in EOC cells led to sharp decrease of cell proliferation and induced S-phase cell cycle arrest. Additionally, GALNT3 suppression significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon GALNT3 suppression, while some tumor suppressor genes were induced. Moreover, GALNT3 downregulation was associated with reduced MUC1 protein expression in EOC cells, probably related to destabilization of the MUC1 protein due to lack of GALNT3 glycosylation activity.Taken together, our data are indicative for a strong oncogenic potential of the GALNT3 gene in advanced EOC and identify this transferase as a novel EOC biomarker and putative EOC therapeutic target. Our findings also suggest that GALNT3 overexpression might contribute to ovarian etiology through aberrant mucin O-glycosylation.
2014-05-22 | GSE52602 | GEO
Project description:Dr. Clausen's laboratory is interested in the structure, biosynthesis and genetic regulation of glycoconjugates, with a major focus on mucins. This laboratory is studying the glycosylation and secretion process of mucins and biological functions involving mucins. This lab is also interested in receptor modulation mediated by glycosylation or through glycosphingolipids. RNA samples from two human pancreatic cell lines. The relevance of the variable expression levels of isoforms belonging to the polypeptide GalNAc-transferase gene-family is still a puzzle to us. The polypeptide GalNAc-transferase gene family is estimated to contain 24 gene-members all participating in the initiation of mucin-type O-glycosylation. It has become apparent that each of these individual isoforms have different tissue distribution profiles and kinetic capabilities. Mucin-type O-glycosylation is thus controlled, and dependent upon the repetoir of expressed GalNAc-transferases in any given organ and cell type at any given time. We have been trying to contribute to the understanding of the ordered process controlling mucin-type O-glycosylation in both normal and malignant models, and are currently investigating a pancreatic cell line model in the lab. The pancreatic tumor cell line ASPC-1 has been found to possess low metastatic potential in mouse models, in contrast to the pancreatic tumor cell line Suit-T2 possessing high metastatic potential. Immunohistochemical analysis of both cell lines, ASPC-1 and Suit-T2, using our monoclonal antibodies to 7 isoforms has revealed great differences in the expression profile of these 7 isoforms in theses two cell lines, and for instance GalNAc-T3 has been found to be highly expressed in Suit-T2 but completely lacking in ASPC-1. Two cell lines: ASPC-1 and Suit-T2 are analyzed with 3 independent replicate prepared for each cell line.
2010-12-11 | E-GEOD-26011 | biostudies-arrayexpress
Project description:Dr. Clausen's laboratory is interested in the structure, biosynthesis and genetic regulation of glycoconjugates, with a major focus on mucins. This laboratory is studying the glycosylation and secretion process of mucins and biological functions involving mucins. This lab is also interested in receptor modulation mediated by glycosylation or through glycosphingolipids. RNA samples from two human pancreatic cell lines. The relevance of the variable expression levels of isoforms belonging to the polypeptide GalNAc-transferase gene-family is still a puzzle to us. The polypeptide GalNAc-transferase gene family is estimated to contain 24 gene-members all participating in the initiation of mucin-type O-glycosylation. It has become apparent that each of these individual isoforms have different tissue distribution profiles and kinetic capabilities. Mucin-type O-glycosylation is thus controlled, and dependent upon the repetoir of expressed GalNAc-transferases in any given organ and cell type at any given time. We have been trying to contribute to the understanding of the ordered process controlling mucin-type O-glycosylation in both normal and malignant models, and are currently investigating a pancreatic cell line model in the lab. The pancreatic tumor cell line ASPC-1 has been found to possess low metastatic potential in mouse models, in contrast to the pancreatic tumor cell line Suit-T2 possessing high metastatic potential. Immunohistochemical analysis of both cell lines, ASPC-1 and Suit-T2, using our monoclonal antibodies to 7 isoforms has revealed great differences in the expression profile of these 7 isoforms in theses two cell lines, and for instance GalNAc-T3 has been found to be highly expressed in Suit-T2 but completely lacking in ASPC-1.
2010-12-11 | GSE26011 | GEO
Project description:Downregulation or gene mutation of MUC6, a major component of gastric mucin, is often identified in human gastric cancers. However, the mechanistic role of MUC6 alteration in gastric carcinogenesis remains unclear. Here, using Muc6-deficient mice, we revealed that dysregulated glycosylation in Muc6-deficient gastric epithelium causes aberrant golgi stress responses, resulting in spontaneous gastric cancer development. Muc6-deficient tumor growth is dependent on MAPK activation, which is mediated by golgi stress-induced golph3 upregulation. Glycomic analysis and lectin-binding assays revealed abnormal expression of mannose-rich N-type glycans in Muc6-deficient gastric tumors. Banana lectin-drug conjugates, which bind to mannose-rich glycans, dramatically suppress mannose-rich murine and human gastric cancer growth. Thus, we propose golgi stress responses and aberrant sugar chains as promising therapeutic targets in gastric cancers accompanied with mucin expression disorder.
2024-08-31 | GSE237822 | GEO
Project description:Downregulation or gene mutation of MUC6, a major component of gastric mucin, is often identified in human gastric cancers. However, the mechanistic role of MUC6 alteration in gastric carcinogenesis remains unclear. Here, using Muc6-deficient mice, we revealed that dysregulated glycosylation in Muc6-deficient gastric epithelium causes aberrant golgi stress responses, resulting in spontaneous gastric cancer development. Muc6-deficient tumor growth is dependent on MAPK activation, which is mediated by golgi stress-induced golph3 upregulation. Glycomic analysis and lectin-binding assays revealed abnormal expression of mannose-rich N-type glycans in Muc6-deficient gastric tumors. Banana lectin-drug conjugates, which bind to mannose-rich glycans, dramatically suppress mannose-rich murine and human gastric cancer growth. Thus, we propose golgi stress responses and aberrant sugar chains as promising therapeutic targets in gastric cancers accompanied with mucin expression disorder.
2024-08-31 | GSE237689 | GEO
Project description:Downregulation or gene mutation of MUC6, a major component of gastric mucin, is often identified in human gastric cancers. However, the mechanistic role of MUC6 alteration in gastric carcinogenesis remains unclear. Here, using Muc6-deficient mice, we revealed that dysregulated glycosylation in Muc6-deficient gastric epithelium causes aberrant golgi stress responses, resulting in spontaneous gastric cancer development. Muc6-deficient tumor growth is dependent on MAPK activation, which is mediated by golgi stress-induced golph3 upregulation. Glycomic analysis and lectin-binding assays revealed abnormal expression of mannose-rich N-type glycans in Muc6-deficient gastric tumors. Banana lectin-drug conjugates, which bind to mannose-rich glycans, dramatically suppress mannose-rich murine and human gastric cancer growth. Thus, we propose golgi stress responses and aberrant sugar chains as promising therapeutic targets in gastric cancers accompanied with mucin expression disorder.
2024-08-31 | GSE237686 | GEO
Project description:Aberrant glycosylation is a characteristic of tumor cells. The expression of certain glycan structures has been associated with poor prognosis. In cervical carcinoma has been reported changes in the gene expression level of some glycogenes that has been associated with lymph invasion. Human papilloma virus (HPV) infection is one of the most important factors to develop cervical cancer. HPV oncoproteins E6 and E7 have been implicated in cervical carcinogenesis. The role of these oncoproteins in glycosylation changes has not been reported. To know the effect of these oncoproteins on glycogene expression we realized a partial silencing of oncogenes E6 and E7 in HeLa cells, we made a microarray expression assay and we identified glycogenes that modified its expression. The analysis showed alteration in some glycosylation pathways, like glycosphingolipid, O-glycan mucin-type, and O-glycan non mucin-type glycosylation. Our results suggest that E6 and E7 oncoproteins could modified glycosylation of structures implicated in proliferation, adhesion, and apoptosis.
2016-12-07 | GSE90930 | GEO
Project description:Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, thus understanding molecular changes associated with EOC progression could lead to the identification of essential therapeutic targets. Glycosylation is a post-translational modification (PTM) that participates in major pathophysiology events, including tumorigenesis. Aberrant mucin-type or O-glycosylation in cancer is frequently attributed to altered expression of different N-acetylgalactosaminyltransferases (GalNAc-Ts). We have previously identified the N-acetylgalactosaminyltransferase 3 (GALNT3) gene as a potential EOC oncogene, possibly implicated in aberrant O-glycosylation in EOC cells. Literature reports are suggestive for genetic and functional redundancy between different GalNAc-Ts, and our previous data were indicative for an induction of the GALNT6 expression upon GALNT3 suppression in EOC cells. Here we show that GALNT3 gene knockout (KO) in the A2780s EOC cells leads to strong GALNT6 upregulation. Moreover, A2780s cell migration, invasion, proliferation and cell cycle analysis were significantly reduced in double GALNT3/T6 gene KO cells compared to single GALNT3 gene KO. Furthermore, MUC1 expression was downregulated in both GALNT3 KO and GALNT3/6 KO, with a more prominent decrease observed in the double KO clone. In vivo studies supported the observed functional redundancy imposed by GALNT6, as animals injected with double GALNT3/T6 KO EOC cell clones displayed a significant increase in survival rates compared to those injected with the control and the GALNT3 KO clones. Collectively our data strongly suggest for possible functional redundancy of the two GalNAc-Ts (GALNT3 and T6) in EOC, with the perspective to use both of these genes as EOC markers and/or therapeutic targets.
2019-05-07 | GSE104861 | GEO
Project description:The identification and characterization of subpopulations of cancer stem cells (CSCs) provide new understandings and possible therapeutic implications in cancer biology. We found the ovarian cancer sphere cells possessed CSCs properties maintained self renewal, drug resistance, and tumorigenesis. Using high-throughput microarray system, we identified common GO terms and pathway signatures significantly enriched in ovarian and breast cancer stem cells. Ovarian and breast cancer cells were cultured in sphere formation conditions, and total RNA from those spheres and conresponding adhered cell was hybridized on Affymetrix microarrays.
2013-11-25 | E-GEOD-43657 | biostudies-arrayexpress