Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA388881 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5641840.fastq.gz | Fastqsanger.gz | |||
| SRR5641841.fastq.gz | Fastqsanger.gz | |||
| SRR5641836.fastq.gz | Fastqsanger.gz | |||
| SRR5641837.fastq.gz | Fastqsanger.gz | |||
| SRR5641838.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:Inappropriate activation of developmental pathways is a well-recognized tumor-promoting mechanism. Here we show that overexpression of the homeoprotein Six1, normally a developmentally restricted transcriptional regulator, increases Transforming Growth Factor-beta (TGF-beta) signaling in mammary carcinoma cells and induces an epithelial to mesenchymal transition (EMT) that is in part dependent on its ability to increase TGF-beta signaling. TGF-beta signaling and EMT have been implicated in metastatic dissemination of carcinoma. Using spontaneous and experimental metastasis mouse models, we demonstrate that Six1 overexpression promotes breast cancer metastasis. In addition, we show that, like its induction of EMT, Six1-induced experimental metastasis is dependent on its ability to activate TGF-beta signaling. Importantly, in human breast cancers Six1 significantly correlates with nuclear Smad3, and thus increased TGF-beta signaling. Further, breast cancer patients whose tumors overexpress Six1 have a shortened time to relapse and metastasis, and an overall decrease in survival. Finally, we show that the effects of Six1 on tumor progression likely extend beyond breast cancer, since its overexpression correlates with adverse outcomes in numerous other cancers, including brain, cervical, prostate, colon, kidney, and liver, amongst others. Our findings argue that Six1, acting through TGF-beta signaling and EMT, is a powerful and global promoter of cancer metastasis.
2010-08-21 | GSE23655 | GEO
Project description:BRMS1L (breast cancer metastasis suppressor 1 like，BRMS1-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--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-β in breast cancer cells. Oncogene. 2013
2014-09-12 | GSE61354 | 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:Epithelial-to-mesenchymal transition (EMT) plays a crucial role in metastasis, which is the leading cause of death in breast cancer patients. We show that Cdc42 GTPase-activating protein (CdGAP) promotes tumor formation and metastasis to lungs in the HER2-positive (HER2+) murine breast cancer model. CdGAP facilitates intravasation, extravasation, and growth at metastatic sites. CdGAP depletion in HER2+ murine primary tumors mediates crosstalk with a Dlc1-RhoA pathway and is associated with a transforming growth factor-β (TGF-β)-induced EMT transcriptional signature. To further delineate the molecular mechanisms underlying the pro-migratory role of CdGAP in breast cancer cells, we searched for CdGAP interactors by performing a proteomic analysis using HEK293 cells overexpressing GFP-CdGAP. We found that CdGAP interacts with the adaptor Talin to modulate focal adhesion dynamics and integrin activation. Moreover, HER2+ breast cancer patients with high CdGAP mRNA expression combined with a high TGF-β-EMT signature are more likely to present lymph node invasion. Our results suggest CdGAP as a candidate therapeutic target for HER2+ metastatic breast cancer by inhibiting TGF-β and Integrin/Talin signaling pathways.
2023-07-14 | PXD043376 | Pride
Project description:Tumor-derived extracellular vesicles (EVs) have been associated with cancer progression and metastasis due to the transfer of bioactive molecules in between the tumor microenvironment. Although Transforming Growth Factor-β (TGF-β) signaling associated molecules have been implicated as cargo of EVs, the role of TGF-β pathway on EV’s biology to promote tumorigenesis is poorly understood. Hence, we aimed to describe the impact of TGF-β signaling on biogenesis and functional transfer of cargo from tumor-derived EVs induced by TGF-β (EV+TGF-β1). To this end, EV-fractions enriched in CD81 or Cholerae toxin B chain (CTB) were isolated from the vesicular secretome fraction (VSF) of human breast cancer and lung adenocarcinoma cells and further characterized.
2025-05-06 | PXD039591 | Pride
Project description:Protein deacetylase SIRT7 is significantly downregulated in lung metastases of human patient and mouse tissues, and predicted metastasis-free survival. To explore the roles of SIRT7 in breast cancer, we analysed the gene expressions in breast cancer BT549 cells with SIRT7 knockdown or not.
2017-06-03 | GSE99596 | GEO
Project description:Transforming growth factor-β (TGF-β) signaling stimulates cell movement and plasticity by inducing epithelial-to-mesenchymal transition (EMT). This process is aberrantly activated in cancer and facilitates tumor cell migration, invasion, metastasis, and therapy resistance. In this study, we identified the lncRNA eSNAI1 (SCREEM2) as a potent activator of TGF-β/SMAD signaling and SNAI1 expression. eSNAI1 depletion reduces TGF-β-induced EMT, migration, in vivo extravasation, stemness, and chemotherapy resistance of breast cancer cells. eSNAI1 promotes TGF-β/SMAD signaling by inhibiting TGF-β type I receptor polyubiquitination and proteasomal degradation. eSNAI1 stimulates the expression of the nearby gene SNAI1, which encodes the EMT transcription factor SNAI1 that facilitates TGF-β/SMAD signaling by retaining the inhibitory SMAD7 in the nucleus. Mechanistically, eSNAI1 acts as an enhancer RNA (eRNA) to potentiate SNAI1 expression through in-cis regulation. Furthermore, we uncovered that eSNAI1 interacts with and reinforces the binding of the co-activator bromodomain-containing protein 4 (BRD4) to the H3 lysine 27 acetylation (H3K27ac)-enriched SNAI1 enhancer region. Our findings identify eSNAI1 as a potent activator of TGF-β signaling and a promising therapeutic target to mitigate overactive TGF-β signaling and EMT in cancer cells.
2025-03-06 | GSE276203 | GEO
Project description:TGF-beta is one of the key cytokines implicated in various disease processes including cancer. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells and in contrast, acts as a pro-tumour cytokine by promoting tumour angiogenesis, immune-escape and metastasis. The effect of TGF-beta on the regulation of gene expression is cell-type specific. In order to identify TGF-beta regulated genes in different cell-types, we followed the expression profiling approach. Keywords: cell type specific response to TGF-beta
2007-05-01 | GSE7661 | GEO
Project description:Purpose: Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of a LncRNA, Rho GTPase Activating Protein 5- Antisense 1 (ARHGAP5-AS1) in breast cancer was investigated. Methods: RNA sequencing was performed to find out dysregulated LncRNAs in MDA-MB-231-LM2 cells. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-β signaling. Results: Compared to MDA-MB-231 cells, the expression of LncRNA ARHGAP5-AS1 (NR_027263) was significantly suppressed in its highly metastatic subtype MDA-MB-231-LM2 cells. Functional study showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-β signaling pathway due to its inhibitory role on SMAD7. Conclusion: Overall, these findings demonstrate that ARHGAP5-AS1 inhibits breast cancer cell migration and could serve as a novel biomarker for breast cancer metastasis and a potent target for the treatment in the future.
2021-05-20 | GSE174717 | GEO