Ontology highlight
ABSTRACT:
PROVIDER: PRJNA903384 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: Esophageal squamous cell carcinoma (ESCC) is a serious malignant tumor, it affects human health. We analyzed the correlation between serum Stathmin levels and ESCC, further elucidated the molecular mechanisms how Stathmin promotes ESCC cell invasion and metastasis. Methods: Stathmin levels in ESCC and healthy control serum was detected by enzyme-linked immunosorbent assay (ELISA), and analyzed the clinical parameters. We established ESCC cells with Stathmin overexpression or knockdown, next evaluated the effects of Stathmin on invasion, metastasis and proliferation in ESCC. The expression levels of the integrin family, focal adhesion kinase (FAK) protein and extracellular signal-regulated kinase (ERK) were detected by immunoblotting. Results: Serum levels of Stathmin were significantly higher in ESCC and associated with lymph node metastasis, tumor stage and size. Furthermore, we found Stathmin promotes migration, invasion and proliferation of ESCC cells in vitro and in vivo. Further study confirmed that the activation of integrinα5β1/FAK/ERK pathway is increased in Stathmin overexpression cells, this pathway contribute to strengthen cell adhesion. Stathmin accelerates the cell motility by enhancing cell adhesion ability. Conclusion: Stathmin may be a potential biomarker for ESCC clinical detection, and it can promotes ESCC cell invasion and metastasis through the integrinα5β1/FAK/ERK pathway. The differentially expressed genes were analyzed by Human Transcriptome Array, and confirmed by RT-PCR.
2016-11-29 | GSE90578 | GEO
Project description:A proportion of superficial esophageal squamous cell carcinoma, a type of less invasive esophageal squamous cell carcinoma (ESCC), would have metastasis after esophagectomy or endoscopic resection with poor prognosis. The purpose of this study was to discover the whole-genome copy number alteration (CNA) profiles of superficial ESCC and compare the CNAs of superficial ESCC patients with and without metastasis after surgery. Thirty eight superficial ESCC cases, including 19 cases with metastasis and 19 cases without metastasis within 5 years after surgery, were analyzed CNAs by Affymetrix OncoScan™ FFPE Assay. A 39-gene signature was initially constructed to identify high risk of metastasis in superficial ESCC patients. In addition, amplification of 11q13.3 (FGF4) and deletion of 9p21.3 (CDKN2A) were identified as recurrent CNAs across all 38 superficial ESCC cases. And amplifications of 3p26.33 (SOX2-OT), 8q24.21 (MYC), 14q21.1 (FOXA1) and deletion of 3p12.1 (GBE1) were identified as recurrent CNAs among metastasis cases only. Our study provided a 39-gene signature tool to identified high risk metastasis in superficial ESCC and suggested that amplifications of SOX2-OT, MYC, FOXA1 genes and deletion of GBE1 gene might play a vital role in metastasis among superficial ESCC.
2017-06-10 | GSE78926 | GEO
Project description:Dysregulation of MOF (MYST1, KAT8), a highly conserved H4K16 acetyltransferase, plays important roles in human cancers. However, its expression and function in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, we report that MOF is highly expressed in ESCC tumors and predicts a worse prognosis. Depletion of MOF in ESCC significantly impedes tumor growth and metastasis both in vitro and in vivo, whereas ectopic expression of MOF but not enzyme inactive mutant (MOF E350Q) promotes ESCC progression, suggesting that MOF acetyltransferase activity is crucial for its oncogenic activity. Further analysis reveals that USP10, a deubiquitinase highly expressed in ESCC, binds to and protects MOF from proteosome-dependent protein degradation. MOF stabilization by USP10 promotes H4K16ac enrichment in the ANXA2 promoter to stimulate ANXA2 transcription, which subsequently activates Wnt/ β-Catenin signaling to facilitate ESCC progression. Our findings highlight a novel USP10/MOF/ANXA2 axis as a promising therapeutic target for ESCC.
2024-01-09 | GSE241066 | GEO
Project description:Objective: Esophageal squamous carcinoma (ESCC) is one of the most common gastrointestinal tumors, and the PI3K/AKT signaling pathway plays a key role in the development of ESCC. circRNAs have been reported to be involved in the regulation of PI3K/AKT signaling, but the underlying mechanisms are unclear. This study aimed to identify protein-coding circRNAs and investigate their function in ESCC. Design: Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. A novel protein encoded by circ-PDE5A was identified by LC-MS/MS. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circ-PDE5A and its encoded PDE5A-500aa novel protein in ESCC. Construction of a nanoplatform for the coupling of circRNAs to investigate the therapeutic translation value of circ-PDE5A. Results: We found that circ-PDE5A expression was downregulated in ESCC cells and tissues, and its low expression was associated with later clinicopathological staging and poorer prognosis. Functionally, circ-PDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding the novel PDE5A-500aa protein, which was identified as a key player in regulating PI3K/AKT signaling activation in ESCC. Mechanistically, the novel PDE5A-500aa protein binds directly to PIK3IP1 and promotes USP14-mediated deubiquitination of the k48-linked polyubiquitin chain at residue K198 of PIK3IP1, thereby attenuating PI3K/AKT pathway in ESCC. In addition, the circ-PDE5A plasmid-coupled reduction-responsive nanoplatform successfully inhibited ESCC growth and metastasis. Conclusions: circ-PDE5A represents an epigenetic mechanism regulating PI3K/ATK signaling and serves as a novel and promising therapeutic target and prognostic marker for ESCC.
2024-01-15 | GSE250413 | GEO
Project description:To identify the candidate exosomal miRNAs involved in ESCC metastasis, we conducted small RNA sequencing to determine the miRNA expression profiles of plasma exosomes from 5 LNM+ and 5 LNM- ESCC patients
2022-10-02 | GSE214259 | GEO
Project description:Objective: Esophageal squamous carcinoma (ESCC) is one of the most common gastrointestinal tumors, and the PI3K/AKT signaling pathway plays a key role in the development of ESCC. circRNAs have been reported to be involved in the regulation of PI3K/AKT signaling, but the underlying mechanisms are unclear. This study aimed to identify protein-coding circRNAs and investigate their function in ESCC. Design: Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. A novel protein encoded by circ-PDE5A was identified by LC-MS/MS. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circ-PDE5A and its encoded PDE5A-500aa novel protein in ESCC. Construction of a nanoplatform for the coupling of circRNAs to investigate the therapeutic translation value of circ-PDE5A. Results: We found that circ-PDE5A expression was downregulated in ESCC cells and tissues, and its low expression was associated with later clinicopathological staging and poorer prognosis. Functionally, circ-PDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding the novel PDE5A-500aa protein, which was identified as a key player in regulating PI3K/AKT signaling activation in ESCC. Mechanistically, the novel PDE5A-500aa protein binds directly to PIK3IP1 and promotes USP14-mediated deubiquitination of the k48-linked polyubiquitin chain at residue K198 of PIK3IP1, thereby attenuating PI3K/AKT pathway in ESCC. In addition, the circ-PDE5A plasmid-coupled reduction-responsive nanoplatform successfully inhibited ESCC growth and metastasis. Conclusions: circ-PDE5A represents an epigenetic mechanism regulating PI3K/ATK signaling and serves as a novel and promising therapeutic target and prognostic marker for ESCC.
2024-01-15 | GSE250323 | GEO
Project description:Human squamous cell cancers are the most common epithelially derived malignancies. One example is esophageal squamous cell carcinoma (ESCC), which is associated with a high mortality rate that is related to a propensity for invasion and metastasis. We report that periostin, a highly expressed cell adhesion molecule, is a key component of a novel tumor invasive signature obtained from an organotypic culture model of engineered ESCC. This tumor invasive signature classifies with human ESCC microarrays, underscoring its utility in human cancer. Genetic modulation of periostin promotes tumor cell migration and invasion as revealed in gain of and loss of function experiments. Inhibition of EGFR signaling and restoration of wild-type p53 function were each found to attenuate periostin, suggesting interdependence of two common genetic alterations with periostin function. Our studies reveal periostin as an important mediator of ESCC tumor invasion and they indicate that organotypic (3D) culture can offer an important tool to discover novel biologic effectors in cancer. Invading and non-invading genetically engineered human esophageal cells with hTERT and EGFR overexpression and p53 mutations were grown in organotypic culture. These invading and non-invading cells were excised using laser-capture microdissection. RNA was isolated and amplified for Affymetrix U133 microarrays. Subsequent microarray analysis & comparison with 2 independent cohorts of primary ESCC tumors revealed upregulation of periostin as gene with highest upregulation found in novel tumor invasive signature in esophageal cancer.
2010-07-08 | E-GEOD-21293 | biostudies-arrayexpress
Project description:Background and aims: Cancer metastasis is the biggest obstacle to esophageal squamous cell carcinoma (ESCC) treatment. At present, understanding of its mechanism remains insufficient. Therefore, an in-depth exploration of the mechanisms of metastasis is crucial for early detection and intervention to reduce metastasis-related mortality. Methods: This study applied single-cell RNA sequencing analysis to investigate lung metastatic ESCC cells isolated from a pulmonary metastasis mouse model at multiple timepoints to characterize early metastatic microenvironment. Results: We identified a small population of parental ESCC KYSE30 cell line (Cluster S) resembled metastasis-initiating cells (MICs) because they could survive and colonize at lung metastatic sites. By comparing differential expression profiles between Cluster S and other subpopulations, we identified a panel of 7 metastasis-initiating signature genes (MIS), including CD44 and TACSTD2, to represent MICs of ESCC. Functional studies demonstrated that Cluster S cells (CD44high) exhibited significantly enhanced cell survival (resistances to oxidative stress and apoptosis), cell migration, invasion, stemness, and in vivo lung metastasis capabilities. Multiplex immunohistochemistry (mIHC) staining of 4 MISs (CD44, S100A14, RHOD, and TACSTD2) in ESCC cell lines and clinical samples found that differential MIS expression scores (dMISs) could predict lymph node metastasis, overall survival and risk of carcinothrombosis. GO and KEGG analyses revealed that CD44high cells were enriched in cell migration, organ development, stress responses, and neuron development, which might be related to the establishment of early metastatic microenvironment. Conclusion: This study identified CD44, S100A14, RHOD, and TACSTD2 as MISs to represent the MICs in ESCC populations and predict patient outcomes. Keywords: ESCC, metastasis-initiating cells, metastasis-initiating signatures, biomarker, scRNA-seq.
2024-08-21 | GSE249057 | GEO
Project description:Background and aims: Cancer metastasis is the biggest obstacle to esophageal squamous cell carcinoma (ESCC) treatment. At present, understanding of its mechanism remains insufficient. Therefore, an in-depth exploration of the mechanisms of metastasis is crucial for early detection and intervention to reduce metastasis-related mortality. Methods: This study applied single-cell RNA sequencing analysis to investigate lung metastatic ESCC cells isolated from a pulmonary metastasis mouse model at multiple timepoints to characterize early metastatic microenvironment. Results: We identified a small population of parental ESCC KYSE30 cell line (Cluster S) resembled metastasis-initiating cells (MICs) because they could survive and colonize at lung metastatic sites. By comparing differential expression profiles between Cluster S and other subpopulations, we identified a panel of 7 metastasis-initiating signature genes (MIS), including CD44 and TACSTD2, to represent MICs of ESCC. Functional studies demonstrated that Cluster S cells (CD44high) exhibited significantly enhanced cell survival (resistances to oxidative stress and apoptosis), cell migration, invasion, stemness, and in vivo lung metastasis capabilities. Multiplex immunohistochemistry (mIHC) staining of 4 MISs (CD44, S100A14, RHOD, and TACSTD2) in ESCC cell lines and clinical samples found that differential MIS expression scores (dMISs) could predict lymph node metastasis, overall survival and risk of carcinothrombosis. GO and KEGG analyses revealed that CD44high cells were enriched in cell migration, organ development, stress responses, and neuron development, which might be related to the establishment of early metastatic microenvironment. Conclusion: This study identified CD44, S100A14, RHOD, and TACSTD2 as MISs to represent the MICs in ESCC populations and predict patient outcomes. Keywords: ESCC, metastasis-initiating cells, metastasis-initiating signatures, biomarker, scRNA-seq.
2024-08-21 | GSE249056 | GEO