MUC1 elevation promote the progress of cervical squamous cell carcinoma through ERK phosphorylation and ITGA2/ITGA3
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ABSTRACT:
PROVIDER: PRJNA1006058 | ENA |
REPOSITORIES: ENA
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Project description:In contrast to the decreasing trends in developed countries, the incidence and mortality rates of cervical cancer in China have increased significantly. Screening and identification of reliable biomarkers and candidate drug targets of cervical cancer are urgent to improve the survival rate and quality of life of patients. In this study, we demonstrated that MUC1 displayed elevation in cervical squamous cell carcinoma (CSCC). The expression of MUC1 was higher in neoplastic compared with non-neoplastic tissues of the cervix, indicated its potential in early diagnosis of cervical squamous cell carcinoma. Next, we explored the regulatory mechanism of MUC1 in CSCC. MUC1 overexpression promoted the proliferation and metastasis abilities of cervical cancer cells. MUC1 could regulate ERK phosphorylation, then upregulated ITGA2 and ITGA3 expression. Further knockdown of ITGA2 and ITGA3 significantly inhibited tumorigenesis of cervical cancer cells. Moreover, we designed a combination drug regimen with MUC1-siRNA and ERK inhibitor in vivo, founding that the combination of drugs achieved better results in animals with xenograft compared with targeting MUC1 alone. Taken together, we discovered a novel regulatory MUC1/ERK/ITGA2/3 pathway in cervical cancer that may serve as potential biomarkers and therapeutic targets in the future.
2023-08-21 | GSE241017 | GEO
Project description:Patients with rare pancreatic neuroendocrine tumors (pNETs) have limited access to effective targeted agents and invariably succumb to progressive disease. MUC1-C is a druggable oncogenic protein linked to driving pan-cancers. There is no known involvement of MUC1-C in pNET progression. The present work was performed to determine if MUC1-C represents a potential target for advancing pNET treatment. We demonstrate that the MUC1 gene is upregulated in primary pNETs that progress with metastatic disease. In pNET cells, MUC1-C drives E2F- and MYC-signaling pathways necessary for survival. Targeting MUC1-C genetically and pharmacologically also inhibits self-renewal capacity and tumorigenicity. Studies of primary pNET tissues further demonstrate that MUC1-C expression associates with (i) advanced NET grade and pathological stage, (ii) metastatic disease, and (iii) decreased disease-free survival. These findings demonstrate that MUC1-C is necessary for pNET progression and is a novel target for treating these rare cancers with anti-MUC1-C agents under clinical development.
2024-05-21 | GSE267722 | GEO
Project description:Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells at different mucosal surfaces including breast and intestine. The MUC1 extracellular domain contains a variable number of tandem repeats (VNTR) of 20 amino acids, which are heavily O-linked glycosylated. Monoclonal antibodies against the MUC1 VNTR can be powerful tools because of their multiplicity of binding and possible applications in the diagnosis and treatment of MUC1-expressing cancers. One such antibody is the hybridoma mouse monoclonal 139H2 which is also widely used as a research tool to study non-cancer MUC1. Here we report direct mass spectrometry-based sequencing of hybridoma-derived 139H2 IgG, which enabled reverse engineering of a recombinant 139H2.
2024-03-18 | PXD043489 | Pride
Project description:During pregnancy, trophoblast cells in the placenta are the only fetal cells in direct contact with the maternal blood and decidua. They have many functions, including transport of nutrients and oxygen, remodelling the uterine arteries, and communicating with maternal cells. Despite their importance in development and in the success of pregnancy, little is known about human trophoblast progenitors and their differentiation. We identify a proliferative trophoblast niche at the base of cytotrophoblast cell columns in first trimester placentas that is characterised by integrin α2 (ITGA2) expression. Pulse-chase experiments with 5-Iodo-2′-deoxyuridine (IdU) imply that these cells can contribute to both villous and extravillous lineages. Importantly, these cells can be isolated by ITGA2 using flow cytometry and express genes from both VCT and EVT. Microarray shows that they display a unique gene signature including NOTCH signalling and mesenchymal characteristics. ITGA2 allows for the first time the study of a pure population of trophoblast progenitor cells.
2018-03-18 | GSE106852 | GEO
Project description:Goal of study: To determine differentially expressed genes with potential roles in tolerance and immunity in MUC1-immunized WT and MUC1.Tg mice WT (C57Bl/6) and MUC1.Tg mice were immunized (i.v.) with dendritic cells loaded with sythetic, human MUC1 peptide. At 24h and 72h splenic RNA from vaccination groups (n=3) was pooled and microarray performed.
2013-01-16 | E-GEOD-43503 | biostudies-arrayexpress
Project description:To determine if overexpression of MUC1 alters the microRNA profile of pancreatic cancer cells S2.013. Comparison of miRNAs differentially regulated in pancreatic cancer cell line S2.013 with and without MUC1 overexpression. MiRCURY LNA microarray was used to determine differential microRNA expression in one replicate of S2.013.Neo (control) cells compared to S2.013.MUC1 (experimental) cells. Confirmation with qRT-PCR was performed on a subset of microRNAs identified as differentially regulated between the two groups.
2013-08-10 | E-GEOD-48185 | biostudies-arrayexpress
Project description:The aberrant overexpression of mucin 1 (MUC1) and human epidermal growth factor receptor 2 (HER2) are often observed in breast cancer. However, the role of concomitant of MUC1/HERR2 in the development of breast cancer has not been fully illustrated. Following analysis public microarray datasets that revealed a correlation of double positive of MUC1 and HER2 to a worse clinical outcome, we generated a mouse model overexpressing both Her2 and MUC1 cytoplasmic domain (MUC1-CD) to investigate their interaction in mammary carcinogenesis. Coexpression of Her2 and MUC1-CD confers growth advantage and promotes the development of spontaneous mammary tumors. Genomic analysis uncovers that enforced expression of MUC1-CD and Her2 induces mammary tumor lineage plasticity which is supported by gene reprogramming and mammary stem cell enrichment. With gain- and loss-of function strategies, we show that coexpression of Her2 and MUC1-CD was associated with down-regulation of TCA cycle genes in tumors. Importantly, the reduction of TCA cycle genes induced by MUC1-CD is is significantly connected to the poor prognosis in HER2+ breast cancer patients. In addition, MUC1 augments Her2 signaling pathway by inducing Her2/Egfr dimerization. These findings collectively demonstrate the vital role of MUC1-CD/Her2 collaboration in shaping mammary tumor landscape and highlight the prognostic and therapeutic implication of MUC1 in patients with Her2+ breast cancer.
2022-03-10 | GSE198239 | GEO
Project description:We identified a novel E2 ubiquitin conjugating activity within the C-terminus domain of MUC1. To determine if E2 ubiquitin conjugating activity of MUC1 is responsible for regulating expression of oncogenic genes we isolated RNA from vector control cells, MUC1 wildtype overexpression cells, and cells that express a serine mutant lacking E2 activity. RNA was isolated from each of the 3 cell lines, S2013.Neo, S2013.MUC1-WT, and S2013.MUC1-Ser. Gene expression was analyzed by spotted microarray and the differences in gene expression were calculated between the cell lines
2016-08-01 | E-GEOD-60339 | biostudies-arrayexpress
Project description:The MUC1 oncoprotein is aberrantly overexpressed in diverse human malignancies including breast and lung cancer. Although MUC1 modulates the activity of several transcription factors, there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of gene families involved in oncogenesis, angiogenesis and extracellular matrix remodeling. A set of experimentally-derived MUC1-induced genes associated with tumorigenesis was applied to the analysis of breast and lung adenocarcinoma cancer databases. A 35-gene MUC1-induced tumorigenesis signature (MTS) predicts significant decreases in both disease-free and overall survival in patients with breast (n = 295) and lung (n = 442) cancers. The data demonstrate that the MUC1 oncoprotein contributes to the regulation of genes that are highly predictive of clinical outcome in breast and lung cancer patients. Experiment Overall Design: To investigate the genes associated with MUC1-CD-induced transformation and tumorigenesis, we performed expression profiling of 3Y1/Vector (empty vector-transfected 3Y1) and 3Y1/MUC1-CD (MUC1-CD-transfected 3Y1) cells growing in vitro, and of 3Y1/MUC1-CD cells growing as tumor xenografts in athymic mice. Cells grown in vitro or as tumor xenografts were lysed to collect total RNA for hybridization with GeneChip® Rat Genome 230 2.0 Arrays.
2009-04-19 | E-GEOD-14337 | biostudies-arrayexpress
Project description:The MUC1 oncoprotein is aberrantly overexpressed in diverse human malignancies including breast and lung cancer. Although MUC1 modulates the activity of several transcription factors, there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of gene families involved in oncogenesis, angiogenesis and extracellular matrix remodeling. A set of experimentally-derived MUC1-induced genes associated with tumorigenesis was applied to the analysis of breast and lung adenocarcinoma cancer databases. A 35-gene MUC1-induced tumorigenesis signature (MTS) predicts significant decreases in both disease-free and overall survival in patients with breast (n = 295) and lung (n = 442) cancers. The data demonstrate that the MUC1 oncoprotein contributes to the regulation of genes that are highly predictive of clinical outcome in breast and lung cancer patients. Keywords: Expression profiling by microarray
2009-04-10 | GSE14337 | GEO