PAI-1 derived cancer-associated fibroblasts in the esophageal squamous cell carcinoma promotes the migration and invasion of cancer cells and macrophages by interaction with LRP1
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PROVIDER: PRJNA599075 | ENA |
REPOSITORIES: ENA
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Project description:Cancer-associated fibroblasts (CAFs) are known to be involved in the progression of various cancers. However, the roles of CAFs in the esophageal squamous cell carcinoma (ESCC) microenvironment remain unclear. We previously co-cultured human bone marrow-derived mesenchymal stem cells (MSCs) with ESCC cells and confirmed the induction of fibroblast activation protein (FAP) in MSCs, which we defined as CAF-like cells. To investigate the roles of CAFs, we performed cDNA microarray analysis between MSCs and CAF-like cells and found that SERPINE1 was highly expressed in CAF-like cells when compared to MSCs. Plasminogen activator inhibitor-1 (PAI-1), encoded by SERPINE1, is generally accepted to play tumor promoting roles and act as a poor prognostic indicator in several cancers. PAI-1 derived from CAF-like cells promoted the cell migration and invasion of ESCC cells by activating Akt and Erk1/2 signaling pathways via low-density lipoprotein receptor related protein 1 (LRP1), the receptor of PAI-1. The higher expression levels of PAI-1 and LRP1 were correlated with the poor prognosis in ESCC patients. These results suggest that PAI-1/LRP1 axis contributes to the progression of ESCC.
2020-07-01 | GSE143138 | GEO
Project description:MIF promotes cell invasion by LRP1-uPAR interaction in pancreatic cancer cells
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Project description:The extracellular activity of Plasminogen activator inhibitor-1 (PAI-1) is well described, acting as an inhibitor of tissue plasminogen activator and urokinase-type plasminogen activator, impacting fibrinolysis. Recent studies have revealed a pro-tumorigenic role of PAI-1 in human cancers, via the regulation of angiogenesis and tumor cell survival. In this study, immunohistochemical staining of 939 human bladder cancer specimens showed that PAI-1 expression levels correlated with tumor grade, tumor stage and overall survival. The typical subcellular localization of PAI-1 is cytoplasmic, but in approximately a quarter of the cases, PAI-1 was observed to be localized to both the tumor cell cytoplasm and the nucleus. To investigate the potential function of nuclear PAI-1 in tumor biology we applied chromatin immunoprecipitation (ChIP)-sequencing, gene expression profiling, and rapid immunoprecipitation mass spectrometry to a pair of bladder cancer cell lines. ChIP-sequencing revealed that PAI-1 can bind DNA at distal intergenic regions, suggesting a role as a transcriptional coregulator. The downregulation of PAI-1 in bladder cancer cell lines caused the upregulation of numerous genes, and the integration of ChIP-sequence and RNA-sequence data identified 57 candidate genes subject to PAI-1 regulation. Taken together, the data suggest that nuclear PAI-1 can influence gene expression programs and support malignancy.
2022-07-20 | GSE201517 | GEO
Project description:The extracellular activity of Plasminogen activator inhibitor-1 (PAI-1) is well described, acting as an inhibitor of tissue plasminogen activator and urokinase-type plasminogen activator, impacting fibrinolysis. Recent studies have revealed a pro-tumorigenic role of PAI-1 in human cancers, via the regulation of angiogenesis and tumor cell survival. In this study, immunohistochemical staining of 939 human bladder cancer specimens showed that PAI-1 expression levels correlated with tumor grade, tumor stage and overall survival. The typical subcellular localization of PAI-1 is cytoplasmic, but in approximately a quarter of the cases, PAI-1 was observed to be localized to both the tumor cell cytoplasm and the nucleus. To investigate the potential function of nuclear PAI-1 in tumor biology we applied chromatin immunoprecipitation (ChIP)-sequencing, gene expression profiling, and rapid immunoprecipitation mass spectrometry to a pair of bladder cancer cell lines. ChIP-sequencing revealed that PAI-1 can bind DNA at distal intergenic regions, suggesting a role as a transcriptional coregulator. The downregulation of PAI-1 in bladder cancer cell lines caused the upregulation of numerous genes, and the integration of ChIP-sequence and RNA-sequence data identified 57 candidate genes subject to PAI-1 regulation. Taken together, the data suggest that nuclear PAI-1 can influence gene expression programs and support malignancy.
2022-07-20 | GSE201515 | GEO
Project description:Esophageal cancer cell sublines with different migration ability
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Project description:Triple-negative breast cancer (TNBC) has a relatively aggressive biological behavior and poor outcome. Our published study showed that PAI-1 could induce the migration and metastasis of TNBC cells. However, the underlying mechanism by which PAI-1 regulates TNBC metastasis has not been addressed. Using microarray analysis of lncRNA expression profiles, we identified a lncRNA SOX2-OT, which is by induced by PAI-1 and could function as an oncogenic lncRNA in TNBC.
2024-05-15 | GSE181202 | GEO
Project description:By using gene chip technology, we can screen esophageal cancer invasion associated genes to understand esophageal squamous carcinoma invasion related mechanisms. Using the Transwell invasion chamber technology to establish human esophageal squamous carcinoma Eca109 and Eca109 - T4 cell lines with different invasion ability. Extracting Eca109 and Eca109-T4 total RNA, reverse transcribed into cDNA probes which labeled with Cy5 and Cy3 fluorescence, then it were hybridized with the Affymetrix gene chip. Using the Genechip- Scanner 3000 scan hybridization signal, and using the SAM 3.0 software analysis and process data.
2014-01-14 | E-GEOD-54041 | biostudies-arrayexpress
Project description:Cellular directed migration is critical to invasion-metastasis cascade of cancer cells. We used in vitro transwell model to screen two esophageal cancer cell lines (KYSE30/180) and obtained two pairs of subpopulations with distinc motiliyt ability. Then we used microarrays to detail the differentially expressed genes and microRNAs between these two cell sublines (30U/D and 180U/D) to identify those responsible for ESCC motility. KYSE30/180 cells were subject to four successive selections using transwell (CORNING, USA). Subpopulations penetrated through membrane (D) or not (U) were harvested respectively for RNA extraction and hybridization on Affymetrix genome and LC Sciences microRNA microarrays
2015-12-31 | E-GEOD-67509 | biostudies-arrayexpress
Project description:Cellular directed migration is critical to invasion-metastasis cascade of cancer cells. We used in vitro transwell model to screen two esophageal cancer cell lines (KYSE30/180) and obtained two pairs of subpopulations with distinc motiliyt ability. Then we used microarrays to detail the differentially expressed genes and microRNAs between these two cell sublines (30U/D and 180U/D) to identify those responsible for ESCC motility.
2015-12-31 | GSE67509 | GEO
Project description:Esophageal cancer is one of the deadliest cancers as patients present at late stages of disease. Frequent gene alterations include the loss of E-cadherin and TGFb receptor type II. The goal of this study was to establish a model of esophageal cancer by introducing dominant-negative mutants of E-cadherin and TGFb receptor II. To analyze the functional consequences and gene expression chages induced by E-cadherin and TGFb receptor type II loss in esophageal cancer. Human esophageal keratinocytes were retrovirally transfected with wild-type full length E-cadherin, dominant-negative E-cadherin and dominant-negative TGFb receptor type II. Grown in organotypic cultures on a collagen/matrigel matrix with embedded fibroblast, the generated cell lines were analyzed for their potential to invade into the underlying matrix. Each cell lines was grown in duplicate in organotypic culture and therefore 2 replicates analyzed. Gene expression changes in invasive versus non-invasive areas were analyzed after RNA isolation using laser-capture microdissection resulting in 2 samples representing a normal esophageal epithelium (Ecad), 2 each of dominant-negative Ecad (Ecyto) non-invasive and invasive. To model the genetic alterations in esophageal cancer dominant-negative E-cadherin and dominant-negative TGFb receptor type II (Ecyto-dnTGFR) were expressed and 2 samples each, non-invasive and invasive, analyzed.
2013-11-12 | E-GEOD-19472 | biostudies-arrayexpress