Role of N-cadherin in epithelial-to-mesenchymal transition and chemosensitivity of colon carcinoma cells
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PROVIDER: PRJNA843101 | ENA |
REPOSITORIES: ENA
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Project description:Increased N-cadherin expression is a pivotal hallmark and step in epithelial-to-mesenchymal transition (EMT), a trans differentiation process activated by colonic tumor cells to increase their spread and survival in a host organism. Although known to be associated with a considerable tumor aggressiveness and worse patient prognosis, exact mechanism(s) linking N-cadherin expression, EMT and aggressive biological phenotype of tumor cells are not entirely clear. In this study we used and compared two different in vitro cell models with varying N-cadherin expression, i.e. colon cancer cell lines HCT8 and SW480 with artificially upregulated expression of N-cadherin, and colon cancer cells with differing N-cadherin levels obtained from patients. Moreover, we have attempted to investigate the relationship between mesenchymal phenotype of cells (here represented by an increased expression of N-cadherin) and the degree of their chemoresistance. We report that although enforced N-cadherin expression changes select morphological and behavioral characteristics of exposed cells, it fails to successfully reprogram cells to the aggressive, chemoresistant phenotype both in vitro as well as in vivo upon implantation into athymic mice. Conversely, primocultures of patient-colonic cells with naturally high levels of N-cadherin expression show fully aggressive and chemoresistant phenotype pertinent to EMT (in vitro and in vivo), with a potential to develop new mutations and in the presence of dysregulated regulatory pathways as represented by investigated miRNA profiles. These results bring new facts concerning the functional axis of N-cadherin expression and related biological features of colon cancer cells and highlight the colon cancer primocultures as useful models for such studies.
2022-06-01 | GSE205027 | GEO
Project description:Substantial experimental evidence has shown that dedifferentiation from an epithelial state to a mesenchymal-like state (EMT) drives tumor cell metastasis. This transition facilitates tumor cells to acquire motility and invasive features. Intriguingly, tumor cells at the metastatic site are primarily epithelial, and it is believed that they re-differentiate back to an epithelial state by a process called mesenchymal to epithelial transition (MET). However, there is little in vivo evidence to support the MET process. In this study we show that clonal epithelial tumor cells undergo EMT (including loss of E-cadherin expression) in the primary tumor over time. At the metastatic site the cells show evidence of MET by re-expression of E-cadherin.
2017-02-09 | GSE81033 | GEO
Project description:(1) Background: N-cadherin expression, epithelial-to-mesenchymal transition (EMT) and aggressive biological phenotype of tumor cells are linked although the underlying mechanisms are not entirely clear. (2) Methods: In this study, we used two different in vitro cell models with varying N-cadherin expression (stabilized lines and primocultures) and investigated their select biological features including the degree of their chemoresistance both in vitro as well as in vivo. (3) Results: We report that although enforced N-cadherin expression changes select morphological and behavioral characteristics of exposed cells, it fails to successfully reprogram cells to the aggressive, chemoresistant phenotype both in vitro as well as in vivo as verified by implantation of those cells into athymic mice. Conversely, primocultures of patient-colonic cells with naturally high levels of N-cadherin expression show fully aggressive and chemoresistant phenotype pertinent to EMT (in vitro and in vivo), with a potential to develop new mutations and in the presence of dysregulated regulatory pathways as represented by investigated miRNA profiles. (4) Conclusions: The presented results bring new facts concerning the functional axis of N-cadherin expression and related biological features of colon cancer cells and highlight colon cancer primocultures as a useful model for such studies.
| S-EPMC9601123 | biostudies-literature
Project description:Our goal was to assess gene expression changes that occur when Lymphoid Enhancer Factor-1 (LEF-1) promotes epithelial-mesenchymal transition (EMT), the primary mechanism of tumor metastasis. To observe this phenomenon without interference from other signaling pathways, we selected DLD1 colon carcinoma cells (ATCC) which contain a mutation in APC. APC is a necessary component of a ubiquitin protein complex (including GSK-3beta, Axin, etc.) that is responsible for degrading cytoplasmic beta-catenin. Therefore, sufficient levels of LEF-1 can be easily activated by forming complexes with the abundant beta-catenin located in the cytoplasm of DLD1 cells. These complexes can then promote transcription of genes that stimulate EMT. We treated DLD1 cells with an adenoviral LEF-1 expression construct, which induced EMT within 48 hours. RNA was then extracted from these cells along with untreated DLD1 cells, then subjected to microarray analysis. From this analysis, we acquired several gene expression profiles by which epithelial colon carcinoma cells transform to an invasive, mesenchymal phenotype to initiate metastasis. Keywords: epithelial-mesenchymal transition, tumor metastasis, cancer progression, epithelial cell plasticity
2006-06-01 | GSE3229 | GEO
Project description:SOX9 suppresses colon cancer via inhibiting epithelial-mesenchymal transition and SOX2 induction
| PRJNA1000611 | ENA
Project description:After 7 days of culture, a sub-population of breast cancer MDAMB231 cells spontaneously detaches the monolayer and starts to grow in suspension, these cells undergo epithelial-mesenchymal transition (EMT), display anoikis resistance and acquire a metastatic phenotype. These cells, in the presence of adherently growing MDAMB231, continue to grow in suspension whereas, seeded in cell-free wells, are able to adhere again and to form E-cadherin positive and vimentin negative new colonies, suggesting the occurrence of mesenchymal-epithelial transition (MET). The expression profiles of these three cell clones (basal, MET and EMT) were investigated by microarray analysis.
2019-03-25 | E-MTAB-6954 | biostudies-arrayexpress
Project description:The aggregation of nephron progenitor cells (NPC) is required to form the nephron precursor renal vesicle (RV) as they undergo the mesenchymal-to-epithelial transition (MET). Canonical Wnt signaling regulates the MET of NPCs via the effector molecule β-catenin. β-catenin acts as a transcriptional co-activator during the differentiation of NPCs, however, if it has any role as an adhesion regulating molecule via the cadherin-catenin complex is currently unknown. Using in vitro NPC culture system with gene editing and modulated Wnt signaling input, we investigated the morphological transition of NPCs and its underlying mechanism modeling the initial step of the MET in vivo. Increasing Wnt signaling input with the small molecule agonist CHIR resulted in the aggregation of NPCs similar to the generation of the nephron anlagen. By removing β- and α-catenin from the NPCs, NPCs are sorted out from these aggregates, demonstrating the key role of the cadherin-catenin complex in the aggregation. β-catenin was essential for the induction, however, the removal of α-catenin did not affect the transcriptional profile of NPCs. Removal of extracellular Ca2+ resulted in the transient loss of cell-cell contacts suggesting the role of cadherins in the aggregation process. The analysis of in vitro bulk RNA-seq cadherin expression profile matched the in vivo cadherin expression profile determined by single-cell RNA-seq. The combined removal of pre-existing and inducible cadherins phenocopied the results of β- and α-catenin KO experiments highlighting the crucial role of the cadherin-catenin complex by multiple lines of evidence. Notably, the induction of NPCs is independent of their aggregation. The in vitro modeling of nephron development provides a mechanistic understanding how cell adhesion is regulated via the cadherin-catenin complex during nephrogenesis.
2024-07-29 | GSE232606 | GEO
Project description:Epithelial-mesenchymal transition (EMT) has been linked to cancer progression and metastatic propensity. The 4T1 tumor is a clinically relevant model of spontaneous breast cancer metastasis. Here we characterize 4T1-derived cell lines for EMT, in vitro invasiveness and in vivo metastatic ability. Contrary to expectations, the 67NR cells, which form primary tumors but fail to metastasize, express vimentin and N-cadherin, but not E-cadherin. 4T1 cells, however, express E-cadherin, are highly migratory and invasive, and metastasize to multiple sites. The 66cl4 metastatic cells display mixed epithelial and mesenchymal markers, but are less migratory and invasive than 67NR cells. These findings demonstrate that the metastatic ability of breast cancer cells does not correlate with genotypic and phenotypic properties of EMT per se, and suggest that other processes may govern metastatic capability. Gene expression analysis also has not identified differences in EMT markers, but has identified several candidate genes that may influence metastatic ability. Keywords: cell type comparison
2008-08-01 | GSE11259 | GEO
Project description:In an effort to develop a genomics-based approach to the prediction of drug response, we have developed an algorithm for classification of cell line chemosensitivity based on gene expression profiles alone. Using oligonucleotide microarrays, the expression levels of 6,817 genes were measured in a panel of 60 human cancer cell lines (the NCI-60) for which the chemosensitivity profiles of thousands of chemical compounds have been determined. We sought to determine whether the gene expression signatures of untreated cells were sufficient for the prediction of chemosensitivity. Gene expression-based classifiers of sensitivity or resistance for 232 compounds were generated and then evaluated on independent sets of data. The classifiers were designed to be independent of the cells' tissue of origin. The accuracy of chemosensitivity prediction was considerably better than would be expected by chance. Eighty-eight of 232 expression-based classifiers performed accurately (with P < 0.05) on an independent test set, whereas only 12 of the 232 would be expected to do so by chance. These results suggest that at least for a subset of compounds genomic approaches to chemosensitivity prediction are feasible. golub-00299 Assay Type: Gene Expression Provider: Affymetrix Array Designs: Hu6800 Organism: Homo sapiens (ncbitax) Tissue Sites: Kidney, Brain, Blood, Lung, Skin, Colon, Breast, Prostate, Ovary Material Types: cell, synthetic_RNA, whole_organism, total_RNA Disease States: Carcinoma, Glioblastoma, Lymphoma, Adenocarcinoma, Melanoma, Amelanotic Melanoma, Large Cell Carcinoma, Precursor Lymphoblastic Leukemia, Carcinosarcoma, Myeloid Leukemia, Plasma Cell Myeloma, Bronchogenic Carcinoma, Chronic Myelogenous Leukemia, Squamous Cell Carcinoma
2015-05-16 | E-GEOD-68936 | biostudies-arrayexpress
Project description:Epithelial ovarian cancer (EOC) accounts for 4% of all cancers in women and is the leading cause of death from gynecologic malignancies. It is well established that cancer invasion and metastasis still represent the major causes of the failure of cancer treatment. Previously, we identified the mannose receptor LY75 (DEC205/CD205) gene as notably hypomethylated in high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. LY75 has been identified as a putative antigen-uptake receptor, which is expressed abundantly on dendritic cells, which are specialist antigen presenting cells to T lymphocytes for the initiation of an immune response. The implication of LY75 in EOC tumorigenesis is currently unknown. Here we show that LY75 is strongly overexpressed in HG serous EOC tumors as compared to normal ovarian tissue. Importantly, shRNA-mediated LY75 knockout in the mesenchymal EOC cells (SKOV3) led to mesenchymal to epithelial transition (MET), associated with overexpression of epithelial markers E-cadherin and EPCAM and loss of expression of mesenchymal markers Fibronectin, N-cadherin Snail1 and Twist1. In addition, LY75 suppression significantly inhibited EOC cell migration and invasion in vitro. However, LY75 knockdown led to enhanced tumor cell dissemination and significantly increased lethality in vivo, in xenograft model of advanced peritoneal EOC. Thus, our findings indicate that LY75 could play an essential role in the mesenchymal-to-epithelial transition (MET) of EOC cells and support the hypothesis that, while epithelial-to-mesenchymal transition (EMT) enables the invasiveness of tumor cells, a MET-associated epithelial phenotype could be essential for their metastatic colonization. To better understand the molecular mechanisms of LY75 gene action in epithelial ovarian cancer (EOC), we employed the Agilent Whole Human Genome microarrays, containing ~ 44,000 genes to identify global gene expression changes upon LY75 suppression in SKOV3 EOC cells. We compared the gene expression of the previously selected shRNA-mediated LY75-knockdown clones sh-S3 and sh-S6 against the corresponding control (ctrl) clone. The microarray experiments were performed in duplicates, as two hybridizations were carried out for each of the LY75-suppressing cell clone against the corresponding control, using a fluorescent dye reversal (dye-swap) technique.
2016-04-01 | E-GEOD-74711 | biostudies-arrayexpress