Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Role of ST6GalNAc-I in immunosuppression and lung adenocarcinoma development

ABSTRACT: Tumors are prone to immune escape by developing strategies to evade immunity. ST6GalNAc-I is an O-glycosyltransferase, which catalyzes the addition of sialic acid onto the first sugar GalNAc (Tn) and results in the formation of Neu5Acα2, 6GalNAc (STn) carbohydrate antigen. SialylTn plays an important role in tumor progression, angiogenesis, and metastasis. RNA sequence analysis was performed using genetically engineered LUAD mouse model tumors (KrasG12D/+; Trp53R172H/+; Ad-Cre (KPA) and KrasG12D/+; Ad-Cre (KA)). We have performed RNA sequence analysis using KPA tumors (N=3), KA tumors (N=3), and littermate control lung tissues (N=3). In comparison to normal lung tissues, several genes were significantly overexpressed in KPA and KA-derived LUAD tumors, including Meg3, Slc7a5, Cxcr1, Awat1, Kng2, Gjb3, Mfi2, and Dlk1. More specifically, St6galnac-I was significantly overexpressed in aggressive-type KPA tumor tissues compared to KA and normal lung tissues. Expression of ST6GalNAc-I is associated with tumor progression and angiogenesis by immunosuppression. Mechanistically, ST6GalNAc-I promotes tumor cell sialylation that impacts tumor angiogenesis by altering mucin MUC5AC. Similarly, ST6GalNAc-I regulates Nectin2 sialylation which leads to immunosuppression and tumor progression. Overall, our study defined that ST6GalNAc-I is a critical molecule for tumor cell sialylation for disease aggressiveness.

ORGANISM(S): Mus musculus

PROVIDER: GSE290957 | GEO | 2025/04/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Targeting stromal cell sialylation reverses T cell mediated immunosuppression in the tumor microenvironment

Project description:Immunosuppressive tumor microenvironments (TME) reduce the effectiveness of immune responses in cancer. Mesenchymal stromal cells (MSC), precursors to cancer-associated fibroblasts (CAFs), dictate tumor progression by enhancing immune cell suppression in colorectal cancer (CRC). Hyper-sialylation of glycans promotes immune evasion in cancer through binding of sialic acids to their receptors, Siglecs, expressed on immune cells that results in inhibition of effector functions. The role of sialylation in dictating MSC/CAF immunosuppression in the TME is unknown. In this study, we show that tumor-conditioned stromal cells have increased sialyltransferase expression, α2,3/6-linked sialic acid and Siglec ligands. Tumor-conditioned stromal cells and CAFs induce exhausted immunomodulatory PD-1, Siglec-7 and Siglec-9-expressing T cell phenotypes. In vivo, targeting stromal cell sialylation reverses stromal cell-mediated immunosuppression, as evidenced by infiltration of CD25 and granzyme B-expressing T cells in the tumor and draining lymph node. Targeting stromal cell sialylation may overcome immunosuppression in the CRC TME.

2023-05-22 | GSE229054 | GEO

Gramd2+ alveolar type I cells can give rise to Kras-induced lung adenocarcinoma

Project description:Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and arises in the distal lung. LUAD encompasses several pathologic subtypes, including solid, lepidic, papillary, micropapillary, acinar and mixed subtypes, each with differing clinical outcomes or biological behavior. Specifically, lepidic histology is associated with improved survival relative to other LUAD histologies. Yet, the molecular and cellular underpinnings of these subtypes are largely unknown. Understanding which cell populations in the distal lung contribute to LUAD could provide insights for the marked heterogeneity in LUAD pathologic features, clinical presentation and responses to therapy.Recent studies have seen tumor-derived epithelial cells with an AT1 transcriptomic cell signature, suggesting AT1 cells may contribute to a subset of LUAD cases. We tested the ability of AT1 cells to give rise to LUAD by inducing KrasG12D, a known oncogenic driver in human LUAD. Activation of KrasG12D in Gram-domain containing 2 (Gramd2)+ AT1 cells gave rise to multiple LUAD lesions, primarily of papillary histology. In contrast, activation of KrasG12D in Sftpc+ AT2 cells resulted in LUAD lesions of lepidic histology. Immunohistochemistry established Gramd2:KrasG12D lesions were of primary lung origin and not metastatic events. Spatial transcriptomic profiling revealed distinct pathway alterations occurring within Gramd2- and Sftpc-derived LUAD. Immunofluorescence confirmed differences observed in the Spatial transcriptomic analysis in expression patterns and distribution of cell-specific markers between cell of origin, while universal upregulation of the Krt8 intermediate cell state marker was observed. Our results are consistent with Gramd2+ AT1 cells serving as a putative cell of origin for LUAD and suggest that LUAD may be a collection of adenocarcinomas that share a common location within the distal lung, but which arise from different cells of origin.

2022-10-19 | GSE215858 | GEO

A novel lncRNA, LUADT1 promotes lung adenocarcinoma proliferation by epigenetic suppression of p27

Project description:Long noncoding RNAs (lncRNAs) are known to regulate the development and progression of various cancers, however, few lncRNAs have been well characterized in lung adenocarcinoma (LUAD). Understanding the expression profile of lncRNAs and protein-coding genes is critical to develop new diagnosis and treatment strategies for LUAD and improving the prognosis of diagnosed patients. Five female LUAD patients with no smoking history were selected to profile lncRNA and protein-coding gene expression with microarrays. Paired tumor tissues and adjacent nontumor tissues were collected and confirmed by pathologists.

2015-03-10 | E-GEOD-66654 | biostudies-arrayexpress

Inflammation mediated by gut microbiome alterations promotes lung cancer development and an immunosuppressed tumor microenvironment

Project description:This study aims to elucidate the impact of gut microbiota alterations on tumorigenesis and immune response in lung adenocarcinoma (LUAD). Using Gprc5a-/- mice as a model, we performed fecal microbiota transfer (FMT) from Gprc5a-/- and Gprc5a-/-; Lcn2-/- donors to investigate the role of gut microbiome changes in modulating tumor growth and the immune microenvironment. Single-cell RNA sequencing (scRNA-seq) was conducted on colonic lamina propria and subcutaneous tumor tissues. Our findings demonstrate that gut microbiota from Lcn2-deficient mice promotes systemic inflammation and immunosuppression, enhancing tumor progression. This study provides insights into the microbiome's influence on LUAD and potential therapeutic strategies targeting microbiome-related pathways.

2024-09-12 | GSE271872 | GEO

788b98a8-5439-490b-826f-20e15db6be36 - samples

Project description:epigenome profiling in tumor tissues and paired normal tissues of LUAD patients and transcriptome profiling in tumor tissues of LUAD patients.

| EGAD00001007066 | EGA

Gene expression profile at single cell level of iron positive and iron negative cells from subcutaneous implanted syngeneic fibrosarcoma tumors in C57BL/6 mice.

Project description:Iron-rich tumor-associated macrophages (iTAMs) are characterized by high intracellular iron, heme metabolism, and expression of the endothelin receptor B. iTAMs promote angiogenesis and immunosuppression in tumors. Heme-mediated degradation of the transcriptional repressor BACH1 induces the iTAM transcriptional program in macrophages.

2024-08-30 | GSE269203 | GEO

Gene expression profile at single cell level of cells from subcutaneous implanted syngeneic fibrosarcoma tumors in C57BL/6 mice injected with autologous erythrocytes suspended in buffered saline

2024-08-30 | GSE268581 | GEO

Hypoxia-induced adaptations of N-glycomes and proteomes in breast cancer cells and their secreted extracellular vesicles

Project description:The hypoxic tumor microenvironment significantly impacts cellular behavior and intercellular communication, with extracellular vesicles (EVs) playing a crucial in promoting angiogenesis, metastasis, and host immunosuppression. Aberrant surface N-glycan expression in EVs is closely associated with cancer progression and metastasis. We hypothesize that hypoxic tumors synthesize specific hypoxia-induced N-glycans, which are packaged into EVs to modulate the tumor microenvironment and drive cancer progression. This study utilized nano-LC-MS/MS to integrate quantitative proteomic and N-glycomic analyses of both cells and EVs derived from the MDA-MB-231 breast cancer cell line, cultured under normoxic and hypoxic conditions. Whole N-glycome and proteome profiling revealed that hypoxia changes the expression of asparagine N-linked glycosylation and glycolysis/gluconeogenesis proteins in cells to altered N-glycosylation for their adaptation to low oxygen conditions. Distinct N-glycan types, high-mannose glycans like Man3 and Man9 were highly abundant in hypoxic cells. On the other hand, alterations in sialylation and fucosylation patterns were observed in hypoxic cells. Furthermore, hypoxia-induced EVs exhibit a signature consisting of mono-antennary structures and specific N-glycans (H4N3F1S2, H3N3F1S0, and H7N4F3S2, H8N4F1S0 and H8N6F1S2), which significantly associated with a poor prognosis for breast tumor, potentially altering interactions within the tumor microenvironment to promote tumorigenesis and metastasis. Our findings provide an overview of N-glycan profiles, particularly under hypoxic conditions, offer insights into potential biomarkers for tracking tumor microenvironment dynamics and for developing precision medicine approaches in oncology.

2024-11-07 | PXD053696 | Pride

Epigenomic profiling and transcriptomic profiling of LUAD patients tumor tissues and tumor adjacent tissues

Project description:To provide an in-depth understanding of the epigenomic heterogeneity of LUAD, we here investigated the H3K27ac histone modification profiles of tumors and adjacent normal lung tissues from 42 LUAD patients and explored the role of epigenetic alterations in LUAD progression. We also investigated transcriptomic alterations among 36 patients tumor tissues.

| EGAS00001005132 | EGA

Targeting stromal cell sialylation reverses T cell mediated immunosuppression in the tumor microenvironment

Project description:Targeting stromal cell sialylation reverses T cell mediated immunosuppression in the tumor microenvironment

| PRJNA952645 | ENA