Project description:Recent findings show that EMT in cancer is dynamic and display a number of intermediate stages along the transition to obtain a high phenotypic and functional cellular plasticity. To comprehend transcriptional regulation among major EMT-transcription factors (EMT-TFs) along the EMT spectrum, we performed gene expression profiles of EMT-TFs (SNAI1/2, ZEB1/2, TWIST1) overexpressing epithelial (PEO1, OVCA420) and intermediate epithelial (OVCA429) ovarian cancer cell clones. Our results show that these factors generate an unidirectional repressive regulation in cells with epithelial phenotype (PEO1, OVCA420), whereas a bidirectional activation regulation in cells with intermediate epithelial phenotype (OVCA429). Microarray data analysis of these EMT-TFs overexpression clones revealed a distinct signature of gene expression for each phenotype and the overlapping gene set show a strong negative correlation with EMT scores, indicating that loss of this gene set is essential to trigger EMT.
Project description:Chemo-resistance to platinum such as cisplatin is critical in the treatment of ovarian cancer. Recent evidences have linked epithelial-mesenchymal transition (EMT) with the drug resistance as a contributing mechanism. The current study explored the connection between cellular responses to cisplatin with EMT in ovarian cancer. 46 ovarian carcinoma cell lines expression data with and without Cisplatin treatment.
Project description:The present study is aimed at detecting and measuring mRNA levels of genes involved in epithelial to mesenchymal transition (EMT) in biological samples, i.e. in peripheral blood samples of colorectal cancer (CRC) patients and healthy controls, to determine the presence of disease, its progression and risk of recurrence.
Project description:Mouse ovarian cancer cells lines were generated from primary tumor tissues, metastatic tumor tissues and in vitro cultured ovarian bursa cells. Gene transcripts from the whole genome were tested using WG6 microarray to compare gene expression level of cells lines with and without Epithelial to Mesenchymal Transition(EMT).
Project description:We showed that in response to chemotherapy, dying cancer cells can secrete spliceosomal components into the extracellular space. These therapy-induced secretomes enriched with spliceosomal components promote the chemoresistance of recipient tumor cells. We demonstrated that spliceosomal proteins SNU13 and SYNCRIP can relocalize from dying tumor cells to recipient tumor cells via extracellular vesicles. To investigate whether the increased abundance of splicing factors could be the reason for the acquisition of a more aggressive phenotype by tumor cells, we got SKOV3 cell lines stably overexpressing SYNCRIP or SNU13. These cell lines were more resistant to cisplatin compared to control cell line expressing empty vector. Next, to investigate how the therapy response is formed in tumor cells with and without overexpression of spliceosomal proteins SNU13 or SYNCRIP, we performed RNAseq analysis of these cells before and 24 hours after cisplatin treatment. Enrichement analyses showed that in response to cisplatin, genes associated with DNA repair and cell cycle regulation were upregulated in cancer cell lines overexpressing SYNCRIP or SNU13 compared with control cells. This study revealed previously unknown signaling molecules in the microenvironment of ovarian cancer that have potential clinical significance.
Project description:Mouse ovarian cancer cells lines were generated from primary tumor tissues, metastatic tumor tissues and in vitro cultured ovarian bursa cells. Gene transcripts from the whole genome were tested using WG6 microarray to compare gene expression level of cells lines with and without Epithelial to Mesenchymal Transition(EMT). Total RNAs were isolated from different cell lines with two time points for each cell line and compare the differentially expressed genes in cell lines with different biological characteristics.
Project description:Myelin protein zero-like 3 (MPZL3) is an Immunoglobulin-containing transmembrane protein with predicted cell adhesion molecule function. Loss of 11q23, where the MPZL3 gene resides, is frequently observed in cancer. Yet the role and consequences of altered MPZL3 expression have not been explored in tumor development and progression. We addressed this in ovarian cancer, where both MPZL3 amplification and deletions are observed in respective subsets of high-grade serous specimens. While high and low MPZL3 expressing populations are similarly observed in primary ovarian tumors from an independent patient cohort, metastatic omental tumors largely display decreased MPZL3 expression, suggesting that MPZL3 loss is associated with metastatic progression. MPZL3 knock-down leads to an increase in EMT gene expression in OVCAR4 and OVCA433 cell lines, a transcript signature that is associated with poor patient outcomes. MPZL3 promotes homotypic cancer cell adhesion in some cell lines, and decreasing MPZL3 expression enhances invasion and clearance of mesothelial cell monolayers. Conversely, MPZL3 loss abrogates cell cycle progression and proliferation. This was associated with increased resistance to cisplatin and olaparib and reduced DNA damage and apoptosis in response to these agents in OVCAR4 cells. Enhanced cisplatin resistance was further validated in vivo. These data demonstrate for the first time that loss of the predicted adhesion molecule MPZL3 results in EMT and decreased proliferation in ovarian cancer. Our study suggests that decreased MPZL3 expression is a phenotype of ovarian cancer tumor progression and metastasis and may contribute to treatment failure in advanced-stage patients.
Project description:Chemo-resistance to platinum such as cisplatin is critical in the treatment of ovarian cancer. Recent evidences have linked epithelial-mesenchymal transition (EMT) with the drug resistance as a contributing mechanism. The current study explored the connection between cellular responses to cisplatin with EMT in ovarian cancer.