E-cadherin suppresses invasion and promotes metastasis in multiple breast cancer models
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA454875 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7108000_1.fastq.gz | Fastqsanger.gz | |||
| SRR7108000_2.fastq.gz | Fastqsanger.gz | |||
| SRR7108001_1.fastq.gz | Fastqsanger.gz | |||
| SRR7108001_2.fastq.gz | Fastqsanger.gz | |||
| SRR7108002_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
Similar Datasets
Project description:E-cadherin (E-cad) mediates cell-cell adhesion and has been proposed to suppress both invasion and metastasis. However, invasive ductal cancers retain E-cad expression in the primary tumor, circulating tumor cells, and distant metastases. We recently demonstrated that cancer cell clusters are efficient metastatic seeds. Since clusters organize through cell-cell adhesion, we tested the requirement for E-cad in genetically engineered mouse models of luminal and basal breast cancer. Loss of E-cad increased invasion and dissemination in 3D culture and in the mammary gland. However, E-cad loss also reduced cancer cell proliferation, survival, tumor cell seeding, and metastatic outgrowth in the lungs. At the transcript level, loss of E-cad was associated with increased apoptosis. Consistent with these results, inhibition of apoptosis partially rescued the metastatic phenotype of E-cad null cancer cells. We therefore propose that E-cad is an invasion suppressor, survival factor, and metastasis promoter in invasive ductal cancers.
2019-06-24 | GSE114011 | GEO
Project description:Metastasis initiates when cancer cells escape from the primary tumor, which requires changes to intercellular junctions. Claudins are transmembrane proteins that form the tight junction, and their expression is reduced in aggressive breast tumors. However, claudins’ roles during breast cancer metastasis remain unclear. We used gain- and loss-of-function genetics in organoids isolated from murine breast cancer models to establish that Cldn7 suppresses invasion and metastasis. Transcriptomic analysis revealed that Cldn7 knockdown induced smooth muscle actin (SMA)-related genes and a broader mesenchymal phenotype. We validated our results in human cell lines, fresh human tumor tissue, bulk RNA-seq, and public single cell RNA-seq data. We consistently observed an inverse relationship between Cldn7 expression and expression of SMA-related genes. Furthermore, knockdown and overexpression of SMA-related genes demonstrated that they promote breast cancer invasion. Our data reveal that Cldn7 suppresses breast cancer invasion and metastasis through negative regulation of SMA-related and mesenchymal gene expression.
2024-09-13 | GSE273512 | GEO
Project description:Vascular endothelial (VE-)cadherin is a homotypic adhesion protein that is expressed selectively by ECs in which it enables formation of tight vessels and regulation of vascular permeability. Since VE-cadherin is also strongly expressed in placental trophoblasts, it is a prime candidate for a molecular mechanism of vascular mimicry by those cells. Here, we show that the VE-cadherin is required for trophoblast migration and endovascular invasion into the maternal decidua. VE-cadherin deficiency results in loss of spiral artery remodeling due to a lack of invasive trophoblasts, leading to decreased flow of maternal blood into the placenta, fetal growth retardation and death. Loss of trophoblast invasion prevents decidualization, extracellular matrix remodeling, and immune cell clearance. These studies identify VE-cadherin as essential for trophoblast migration and coordination of decidual changes during endovascular invasion. They further suggest endothelial proteins such as VE-cadherin that are expressed by trophoblasts may play functionally distinct roles that do not simply mimic those in ECs.
2021-11-30 | GSE189408 | GEO
Project description:In this study we want to compare the expression profiles of E-cadherin high and low tumor cells from 4 different mice with breast cancer brain metastasis. We used a breast cancer brain metastasis model derived from the PyMT E-cadherin-mCFP breast cancer model (Beerling et al. Cell Reports 2016) and FACS sorted samples based on endogenous E-cadherin-mCFP expression.
2022-07-15 | GSE199775 | GEO
Project description:PRSS8 Suppresses Colorectal Carcinogenesis and Metastasis.
| PRJNA475479 | ENA
Project description:VE-cadherin is essential for trophoblast migration and endovascular invasion
| PRJNA782961 | ENA
Project description:Purpose: Despite that androgen-deprivation therapy results in long-lasting responses, the disease inevitably progresses to metastatic castration-resistant prostate cancer. In this study, we identified miR-33b-3p as a suppressor of metastasis in prostate cancer. miR-33b-3p was significantly reduced in prostate cancer tissues, and the low expression of miR-33b-3p was correlated with poor overall survival of prostate cancer patients. Overexpression of miR-33b-3p inhibited both migration and invasion of highly metastatic prostate cancer cells whereas antagonizing miR-33b-3p promoted those processes in lowly metastatic cells. The in vivo results demonstrate that miR-33b-3p suppresses metastasis of tail vein inoculated prostate cancer cells to lung, liver, and lymph node in mice. DOCK4 was validated as the direct target of miR-33b-3p. miR-33b-3p decreased the expression of DOCK4 and restoration of DOCK4 could rescue miR-33b-3p inhibition on cell migration and invasion. Moreover, downregulation of miR-33b-3p was induced by bortezomib, the clinically used proteasome inhibitor, and overexpression of miR-33b-3p rescued the insufficient inhibition of bortezomib on migration and invasion in prostate cancer cells. Collectively, our findings demonstrate that miR-33b-3p suppresses metastasis by targeting DOCK4 in prostate cancer. Our results suggest that enhancing miR-33b-3p expression may provide a promising therapeutic strategy for overcoming that proteasome inhibitor’s poor efficacy against metastatic prostate cancer.
2021-09-08 | GSE183428 | GEO
Project description:BRMS1L (breast cancer metastasis suppressor 1 likeM-oM-<M-^LBRMS1-like) is a component of the SIN3A-HDAC corepressor complex that suppresses target gene transcription. Here, we show that reduced BRMS1L in breast cancer tissues is associated with tumor metastasis and poor patient survival. Functionally, BRMS1L inhibits migration and invasion of breast cancer cells by inhibiting epithelial-mesenchymal transition (EMT). These effects are mediated by epigenetic silencing of FZD10, a receptor for Wnt signaling, by facilitating the recruitment of HDAC1 to its promoter and enhancing histone H3K9 deacetylation. Consequently, BRMS1L-induced FZD10 silencing inhibits aberrant activation of WNT3-FZD10-M-oM-^AM-"-catenin signaling. Furthermore, BRMS1L is a target of miR-106b and miR-106b upregulation leads to BRMS1L reduction in breast cancer cells. RNAi-mediated silencing of BRMS1L expression promotes metastasis of breast cancer xenografts in immunocompromised mice, while ectopic BRMS1L expression inhibits metastasis. Therefore, BRMS1L provides an epigenetic regulation of Wnt signaling in breast cancer cells and acts as a breast cancer metastasis suppressor. Ther transfection analysis used here were further desxribed in Chang Gong, eta al.2013. miR-106b expression determines the proliferation paradox of TGF-M-NM-2 in breast cancer cells. Oncogene. 2013 A two chip study using total RNA recovered from MDA-MB-231 breast cancer cells transfected with negative control vector or vector overexpressing BRMS1L for 24 hours. Each chip measures the expression 45033 genes were collected from the authoritative data source including NCBI.
2014-09-12 | E-GEOD-61354 | biostudies-arrayexpress
Project description:Homeodomain-interacting protein kinase 2 (HIPK2), a well-known tumor suppressor, exhibits contradictory expression patterns in different cancers. This study was performed to reveal the potential mechanism of HIPK2 involvement in oral squamous cell carcinoma (OSCC) metastasis. High throughput RNA-sequencing was used to detect the dysregulated signaling pathways in HIPK2 deficiency OSCC cells. Transwell assay and lymphatic metastatic orthotopic mouse model assay were performed to identify the effect of HIPK2 on tumor invasion. Western blotting and luciferase reporter assay were performed to examine the HIPK2/P53/E-Cadherin axis in OSCC. We observed that depletion of HIPK2 promoted tumor cell invasion in vitro and facilitated cervical lymph node metastasis in vivo. According to mRNA-sequencing, pathways closely related to tumor invasion were notably activated. HIPK2 was found to trigger E-Cadherin expression by mediating P53, which directly targets the CDH1 (coding E-Cadherin) promoter. Restoring P53 expression rescued the E-Cadherin suppression induced by HIPK2 deficiency. Together, the depletion of HIPK2 expression promoted OSCC metastasis by suppressing the P53/E-Cadherin axis, which might be a promising target for anti-cancer therapies.
2021-01-11 | GSE158262 | GEO
Project description:Alterations in the cadherin-catenin adhesion complexes are involved in tumor initiation, progression and metastasis. However, the functional implication of distinct cadherin types in breast cancer biology is still poorly understood. Methods: To compare the functional role of E-cadherin and P-cadherin in invasive breast cancer, we stably transfected these molecules into the MDA-MB-231 cell line, and investigated their effects on motility, invasion and gene expression regulation. Expression of either E- and P-cadherin significantly increased cell aggregation and induced a switch from fibroblastic to epithelial morphology. Although expression of these cadherins did not completely reverse the mesenchymal phenotype of MDA-MB-231 cells, both E- and P-cadherin decreased fibroblast-like migration and invasion through extracellular matrix in a similar way. Moreover, microarray gene expression analysis of MDA-MB-231 cells after expression of E- and P-cadherins revealed that these molecules can activate signaling pathways leading to significant changes in gene expression. Although the expression patterns induced by E- and P-cadherin showed more similarities than differences, 40 genes were differentially modified by the expression of either cadherin type. Microarray gene expression analysis of MDA-MB-231 cells after expression of E- and P-cadherins using different clones for each conditions to reveal that these molecules can activate signaling pathways leading to significant changes in gene expression
2010-06-19 | E-GEOD-13362 | biostudies-arrayexpress