Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-seq of NIC+,CdGAPwt/wt and NIC+,CdGAPfx/fx tumors

ABSTRACT: CdGAP/ARHGAP31 is a molecular target of TGFb-mediated EMT and required for Her2-positive breast cancer growth and metastasis Metastasis is the leading cause of death in breast cancer patients. The epithelial-to-mesenchymal transition (EMT) has a crucial role in metastasis and is highly critical for tumor cell dissemination. CdGAP/ARHGAP31 is highly expressed in breast cancer tissues and is associated with poor clinical outcome in breast cancer patients. CdGAP cooperates in a GAP-independent manner with the transcriptional repressor Zeb2 to function as a critical modulator of breast cancer through repression of E-cadherin transcription. In this study, we used a murine model of Her2+ breast cancer to investigate further the role of CdGAP in breast tumorigenesis. We found that CdGAP was essential for tumor formation and metastasis to the lungs in the Her2+ mouse breast cancer model. We determined that CdGAP is required for intravasation and growth at the metastatic sites. By using global gene expression approaches, we found that CdGAP depletion in Her2+ primary tumors was associated with an EMT signature, including a decreased expression of the metastatic factor claudin-2 and an increase in E-cadherin expression. In Her2+ breast cancer cells, CdGAP expression is positively regulated by the TGFb canonical pathway in a smad-dependent manner and regulates cell proliferation, migration, invasion, and adhesion. CdGAP was found to interact with the focal adhesion protein Talin and regulates focal adhesion dynamics in breast cancer cells. Collectively, CdGAP appears as a potential anti-metastatic target for the treatment of Her2+ breast cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE167457 | GEO | 2023/07/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

CdGAP is a Talin-binding protein and a target of TGF-β signaling that promotes HER2-positive breast cancer growth and metastasis

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

RNA-seq of MMTV-Neu AXL KO tumor grafts in FVB

Project description:AXL is activated by its ligand GAS6 and is expressed in triple-negative breast cancer cells. We report that AXL is also detected in HER2+ breast cancer specimens where its expression correlates with poor patients’ survival. Using murine models of HER2+ breast cancer, AXL, but not Gas6, was found essential for metastasis. We determined that AXL is required for intravasation, extravasation and growth at the metastatic site. AXL is expressed in HER2+ cancers displaying EMT signatures and contributes to sustain EMT in murine tumors. Interfering with AXL in patient-derived xenograft impaired TGF-β-induced cell invasion. Lastly, pharmacological inhibition of AXL decreased the metastatic burden of mice developing HER2+ breast cancer. Our data identify AXL as a potential co-therapeutic target during the treatment of HER2+ breast cancers to limit metastasis.

2018-05-01 | GSE102369 | GEO

RNA-seq of MMTV-Neu AXL KO tumors

2018-05-01 | GSE102368 | GEO

Cell-type restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing

Project description:Tumor metastasis remains the major cause of cancer-related death, but its molecular basis is still not well understood. Here we uncovered a splicing-mediated pathway that is essential for breast cancer metastasis. We show that the RNA-binding protein hnRNPM promotes breast cancer metastasis by activating the switch of alternative splicing that occurs during epithelial-mesenchymal transition (EMT). Genome-wide deep sequencing analysis suggests that hnRNPM potentiates TGFb signaling and identifies CD44 as a key downstream target of hnRNPM. hnRNPM ablation prevents TGFb-induced EMT and inhibits breast cancer metastasis in mice, whereas enforced expression of the specific CD44s splice isoform overrides the loss of hnRNPM and permits EMT and metastasis. Mechanistically, we demonstrate that the ubiquitously expressed hnRNPM acts in a mesenchymal-specific manner to precisely control CD44 splice isoform switching during EMT. This restricted cell-type activity of hnRNPM is achieved by competition with ESRP1, an epithelial-splicing regulator that binds to the same cis-regulatory RNA elements and is repressed during EMT. Importantly, hnRNPM is associated with aggressive breast cancer and correlates with increased CD44s in patient specimens. These findings demonstrate a novel molecular mechanism through which tumor metastasis is endowed by the hnRNPM-mediated splicing program. RNAseq for control, hnRNPM siRNA treated lung metastatic LM2 clonal line, derived from the mesenchymal MDA-MB-231 cells

2014-06-03 | E-GEOD-57243 | biostudies-arrayexpress

Role of epithelial to mesenchymal transition (EMT) in spontaneous breast cancer metastasis

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

A kinome-wide high-content siRNA screen identifies MEK5-ERK5 signaling as critical for breast cancer cell EMT and metastasis

Project description:We have employed a high-content microscopy screen in combination with a kinome and phosphatome-wide siRNA library to identify signaling pathways underlying an EMT of murine mammary epithelial cells and breast cancer cells. This screen identified the MEK5-ERK5 axis as a critical player in TGFb-mediated EMT. Suppression of MEK5-ERK5 signaling completely prevented the morphological and molecular changes occurring during a TGFb-induced EMT and, conversely, forced highly metastatic breast cancer cells into a differentiated epithelial state. Inhibition of MEK5-ERK5 signaling also repressed breast cancer cell migration and invasion and substantially reduced lung metastasis without affecting primary tumor growth. The results suggest that the MEK5-ERK5 signaling axis plays an important role in the induction and maintenance of breast cancer cell migration and invasion and thus represents an exploitable target for the pharmacological inhibition of cancer cell metastasis.

2018-05-17 | GSE100403 | GEO

Transcription profiling of mouse BALB/c strain animals injected with breast cancer 4T1-derived cells to investigate the role of epithelial to mesenchymal transition (EMT) in spontaneous breast cancer metastasis

2009-03-07 | E-GEOD-11259 | biostudies-arrayexpress

Oct4 affects E-cadherin expression via regulating Rnd1 associated cytoskeleton rearrangement in breast cancer cells

Project description:Oct4, a key transcription factor for maintaining the pluripotency and self-renewal of stem cells has been reported previously. It also plays an important role in tumor proliferation and apoptosis, but the role of Oct4 been in tumor metastasis is still not very clear. Here, we found that ectopic expression of Oct4 in breast cancer cells can inhibit their migration and invasion. Detailed examinations revealed that Oct4 up-regulates expression of E-cadherin, indicative of its inhibitory role in epithelial-mesenchymal transition (EMT). RNA-sequence assay showed that Oct4 down-regulates expression of Rnd1. As an atypical Rho protein, Rnd1 can affect cytoskeleton rearrangement and regulate cadherin-based cell-cell adhesion by antagonizing the typical Rho protein, RhoA. Ectopic expression of Rnd1 in MDA-MB-231 cells changes cell morphology which influences cell adhesion and increases migration. It is reported that EMT is accompanied by cytoskeleton remodeling, we hypothesized that Rnd1 may play a role in regulating EMT. Over-expression of Rnd1 can partly rescue the inhibitory effects induced by Oct4, not only migration and invasion, but also in E-cadherin level and cellular morphology. Furthermore, silencing of Rnd1 can up-regulate the expression of E-cadherin in MDA-MB-231 cells. These results present evidence that ectopic expression of Oct4 increases E-cadherin and inhibits metastasis, effects which may be related to Rnd1 associated cell-cell adhesion in breast cancer cells. Examination of mRNA profiles in MDA-MB-231 cells with OCT4 overexpressing

2014-01-25 | E-GEOD-54392 | biostudies-arrayexpress

MTflEcad I80 and MTflEcad DI150 cells, long-term treated murine derived breast cancer cell lines with H2O2

Project description:Background: Epithelial-mesenchymal transition (EMT) has been implicated in metastasis, drug resistance, survival under stress and also conferring stem cell-like traits to cancer cells. We have aimed at exploring the crosstalk between ROS and an EMT induced by TGFb in breast cancer cells. Methods: We observed that cells exposed to TGFb displayed a decrease of ROS levels. To identify the antioxidant pathways activated during EMT, we investigated the effect of long-term oxidative stress, for example by H2O2 (80 µM and 150 µM), on MTflECad epithelial cells derived from the MMTV-Neu mouse model. Results: We show that long-term treated MTflEcad epithelical cells with H2O2 display both higher migratory capability and tumorigenicity. Furthermore, we identified an activation of the Nrf2 transcription factor, master regulator of the antioxidant response, in H2O2-resistant cells, as well as in TGFb-induced mesenchymal cells. Conclusion: In this study we report the criticial role of the Nrf2-mediated glutathione metabolism in the protection of metastatic breast cancer cells from ferroptosis. Therapeutic targeting of antioxidant pathways may thus be beneficial for patients with metastatic disease.

2022-10-15 | GSE187476 | GEO

Py2T C40 and Py2T I60 cells, long-term treated murine derived breast cancer cell lines with H2O2

Project description:Background: Epithelial-mesenchymal transition (EMT) has been implicated in metastasis, drug resistance, survival under stress and also conferring stem cell-like traits to cancer cells. We have aimed at exploring the crosstalk between ROS and an EMT induced by TGFb in breast cancer cells. Methods: We observed that cells exposed to TGFb displayed a decrease of ROS levels. To identify the antioxidant pathways activated during EMT, we investigated the effect of long-term oxidative stress, for example by H2O2 (40 µM and 60 µM), on Py2T epithelial cells derived from the MMTV-PyMT mouse model. Results: We show that long-term treated Py2T epithelical cells with H2O2 display both higher migratory capability and tumorigenicity. Furthermore, we identified an activation of the Nrf2 transcription factor, master regulator of the antioxidant response, in H2O2-resistant cells, as well as in TGFb-induced mesenchymal cells. Conclusion: In this study we report the criticial role of the Nrf2-mediated glutathione metabolism in the protection of metastatic breast cancer cells from ferroptosis. Therapeutic targeting of antioxidant pathways may thus be beneficial for patients with metastatic disease.

2022-10-15 | GSE187364 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data