The Cdc42/Rac1 regulator CdGAP is a novel E-cadherin transcriptional co-repressor with Zeb2 in breast cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA707409 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13883868_1.fastq.gz | Fastqsanger.gz | |||
| SRR13883868_2.fastq.gz | Fastqsanger.gz | |||
| SRR13883869_1.fastq.gz | Fastqsanger.gz | |||
| SRR13883869_2.fastq.gz | Fastqsanger.gz | |||
| SRR13883870_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:The loss of E-cadherin causes dysfunction of the cell-cell junction machinery, which is an initial step in epithelial-to-mesenchymal transition (EMT), facilitating cancer cell invasion and the formation of metastases. A set of transcriptional repressors of E-cadherin (CDH1) gene expression, including Snail1, Snail2 and Zeb2 mediate E-cadherin down-regulation in breast cancer. However, the molecular mechanisms underlying the control of E-cadherin expression in breast cancer progression remain largely unknown. Here, by using global gene expression approaches, we uncover a novel function for Cdc42 GTPase-activating protein (CdGAP) in the regulation of expression of genes involved in EMT. We found that CdGAP used its proline-rich domain to form a functional complex with Zeb2 to mediate the repression of E-cadherin expression in ErbB2-transformed breast cancer cells. Conversely, knockdown of CdGAP expression led to a decrease of the transcriptional repressors Snail1 and Zeb2, and this correlated with an increase in E-cadherin levels, restoration of cell-cell junctions, and epithelial-like morphological changes. In vivo, loss of CdGAP in ErbB2-transformed breast cancer cells impaired tumor growth and suppressed metastasis to lungs. Finally, CdGAP was highly expressed in basal-type breast cancer cells, and its strong expression correlated with poor prognosis in breast cancer patients. Together, these data support a previously unknown nuclear function for CdGAP where it cooperates in a GAP-independent manner with transcriptional repressors to function as a critical modulator of breast cancer through repression of E-cadherin transcription. Targeting Zeb2-CdGAP interactions may represent novel therapeutic opportunities for breast cancer treatment.
2021-06-01 | GSE168426 | GEO
Project description:The loss of E-cadherin causes dysfunction of the cell-cell junction machinery, which is an initial step in epithelial-to-mesenchymal transition (EMT), facilitating cancer cell invasion and the formation of metastases. A set of transcriptional repressors of E-cadherin (CDH1) gene expression, including Snail1, Snail2 and Zeb2 mediate E-cadherin down-regulation in breast cancer. However, the molecular mechanisms underlying the control of E-cadherin expression in breast cancer progression remain largely unknown. Here, by using global gene expression approaches, we uncover a novel function for Cdc42 GTPase-activating protein (CdGAP) in the regulation of expression of genes involved in EMT. We found that CdGAP used its proline-rich domain to form a functional complex with Zeb2 to mediate the repression of E-cadherin expression in ErbB2-transformed breast cancer cells. Conversely, knockdown of CdGAP expression led to a decrease of the transcriptional repressors Snail1 and Zeb2, and this correlated with an increase in E-cadherin levels, restoration of cell-cell junctions, and epithelial-like morphological changes. In vivo, loss of CdGAP in ErbB2-transformed breast cancer cells impaired tumor growth and suppressed metastasis to lungs. Finally, CdGAP was highly expressed in basal-type breast cancer cells, and its strong expression correlated with poor prognosis in breast cancer patients. Together, these data support a previously unknown nuclear function for CdGAP where it cooperates in a GAP-independent manner with transcriptional repressors to function as a critical modulator of breast cancer through repression of E-cadherin transcription. Targeting Zeb2-CdGAP interactions may represent novel therapeutic opportunities for breast cancer treatment.
2017-08-22 | GSE86301 | GEO
Project description:Cadherin-12 regulates neurite outgrowth through PKA/Rac1/Cdc42 pathway in cortical neurons
| PRJNA759560 | ENA
Project description:Cadherins play an important role in tissue homeostasis, as they are responsible for cell-cell adhesion during embryogenesis, tissue morphogenesis, and differentiation. In this study, we identified Cadherin-12 (CDH12), which encodes a type II classical cadherin, as a gene to promote neurite outgrowth in a vitro model consist of neurons with differentiated intrinsic growth ability. First, the effects of CDH12 on neurons were evaluated by RNA interference, and the result indicated that the knock down of CDH12 expression restrained the axon extension of E18 neurons. The transcriptome profile of the neurons with or without siCDH12 treatment revealed a set of pathways positively correlated with the effect of CDH12 on neurite outgrowth. We further revealed that CDH12 affected Rac1/Cdc42 phosphorylation in PKA dependent manner by testing with H-89 and 8-Bromo-cAMP sodium salt. Moreover, we investigated the expression of CDH12 in brain, spinal cord, and dorsal root ganglion during development by using immunofluorescence staining. Thereafter, we explored the effects of CDH12 on neurite outgrowth in vivo. A zebrafish model of CDH12 knockdown was established by using NgAgo-gDNA system and registered the vital role of CDH12 in peripheral neurogenesis. In summary, our study is the first to report the effect of CDH12 on axonal extension in vitro and in vivo and we provided a preliminary explanation for the mechanism.
2021-12-09 | GSE183174 | GEO
Project description:The loss of E-cadherin causes dysfunction of the cell-cell junction machinery, which is an initial step in epithelial-to-mesenchymal transition (EMT), facilitating cancer cell invasion and the formation of metastases. A set of transcriptional repressors of E-cadherin (CDH1) gene expression, including Snail1, Snail2 and Zeb2 mediate E-cadherin downregulation in breast cancer. However, the molecular mechanisms underlying the control of E-cadherin expression in breast cancer progression remain largely unknown. Here, by using global gene expression approaches, we uncover a novel function for Cdc42 GTPase-activating protein (CdGAP) in the regulation of expression of genes involved in EMT. We found that CdGAP used its proline-rich domain to form a functional complex with Zeb2 to mediate the repression of E-cadherin expression in ErbB2-transformed breast cancer cells. Conversely, knockdown of CdGAP expression led to a decrease of the transcriptional repressors Snail1 and Zeb2, and this correlated with an increase in E-cadherin levels, restoration of cell-cell junctions, and epithelial-like morphological changes. In vivo, loss of CdGAP in ErbB2-transformed breast cancer cells impaired tumor growth and suppressed metastasis to lungs. Finally, CdGAP was highly expressed in basal-type breast cancer cells, and its strong expression correlated with poor prognosis in breast cancer patients. Together, these data support a previously unknown nuclear function for CdGAP where it cooperates in a GAP-independent manner with transcriptional repressors to function as a critical modulator of breast cancer through repression of E-cadherin transcription. Targeting Zeb2-CdGAP interactions may represent novel therapeutic opportunities for breast cancer treatment.
| S-EPMC5423781 | biostudies-literature
Project description:Bergmann glia (BG) are important in the inward type of radial migration of cerebellar granule neurons (CGNs). However, details regarding the functions of Cdc42 and Rac in BG for radial migration of CGN are unknown. To examine the roles of Cdc42 and Rac in BG during cerebellar corticogenesis, mice with a single deletion of Cdc42 or Rac1 and those with double deletions of Cdc42 and Rac1 under control of the glial fibrillary acidic protein (GFAP) promoter: GFAP-Cre;Cdc42flox/flox (Cdc42-KO), GFAP–Cre;Rac1flox/flox (Rac1-KO), and GFAP-Cre;Cdc42 flox/flox;Rac1flox/flox (Cdc42/Rac1-DKO) mice, were generated. Both Cdc42-KO and Rac1-KO mice, but more obviously Cdc42-KO mice, had disturbed alignment of BG in the Purkinje cell layer (PCL). We found that Cdc42-KO, but not Rac1-KO, induced impaired radial migration of CGNs in the late phase of radial migration, leading to retention of CGNs in the inferior half of the molecular layer (ML). Cdc42-KO, but not Rac1-KO, mice also showed aberrantly aligned Purkinje cells (PCs). These phenotypes were exacerbated in Cdc42/Rac1-DKO mice. Alignment of BG radial fibers in the ML and BG endfeet at the pial surface of the cerebellum evaluated by GFAP staining was disturbed and weak in Cdc42/Rac1-DKO mice, respectively. Our data indicate that that Cdc42 and Rac, but predominantly Cdc42, in BG play important roles during the late phase of radial migration of CGNs. We also report here that Cdc42 is involved in gliophilic migration of CGNs, in contrast to Rac, which is more closely connected to regulating neurophilic migration.
2018-01-01 | GSE106141 | GEO
Project description:Objectives: We studied the signal transduction of atrial structural remodelling that contributes to the pathogenesis of atrial fibrillation (AF). Backround: Fibrosis is a hallmark of arrhythmogenic structural remodelling but the underlying molecular mechanisms are incompletely understood. Methods: We performed transcriptional profiling of left atrial myocardium (LA) from patients with AF and sinus rhythm (SR) and applied cultured primary cardiac cells and transgenic mice with overexpression of constitutively active V12Rac1 (RacET) who develop AF at old age to characterize mediators of the signal transduction of atrial remodeling. Results: LA from patients with AF showed a marked upregulation of connective tissue growth factor (CTGF) expression compared SR patients. This was associated with increased fibrosis, NADPH-oxidase-, Rac1- and RhoA activity, upregulation of N-cadherin and connexin 43 (Cx43) expression and increased angiotensin II tissue concentration. In neonatal rat cardiac myocytes and -fibroblasts, a specific small molecule inhibitor of Rac1 or simvastatin completely prevented the angiotensin II induced upregulation of CTGF, Cx43 and N-cadherin expression. Transfection with small-inhibiting CTGF RNA blocked Cx43 and N-cadherin expression. RacET mice showed upregulation of CTGF, Cx43 and N-cadherin protein expression. Inhibition of Rac1 by oral statin treatment prevented these effects, identifying Rac1 as a key regulator of CTGF in vivo. Conclusion: The data identify CTGF as an important mediator of atrial structural remodelling during AF. Angiotensin II activates CTGF via activation of Rac1 and NADPH oxidase, leading to upregulation of Cx43, N-cadherin and interstitial fibrosis and therefore contributing to the signal transduction of atrial structural remodelling. Array design study consists of 5 Atrial Fibrillation patients and matched 5 samples of patients in sinus rhythm (controls).
2010-02-21 | E-GEOD-14975 | biostudies-arrayexpress
Project description:Bergmann glia (BG) are important in the inward type of radial migration of cerebellar granule neurons (CGNs). However, details regarding the functions of Cdc42 and Rac in BG for radial migration of CGN are unknown. To examine the roles of Cdc42 and Rac in BG during cerebellar corticogenesis, mice with a single deletion of Cdc42 or Rac1 and those with double deletions of Cdc42 and Rac1 under control of the glial fibrillary acidic protein (GFAP) promoter: GFAP-Cre;Cdc42flox/flox (Cdc42-KO), GFAP–Cre;Rac1flox/flox (Rac1-KO), and GFAP-Cre;Cdc42 flox/flox;Rac1flox/flox (Cdc42/Rac1-DKO) mice, were generated. Both Cdc42-KO and Rac1-KO mice, but more obviously Cdc42-KO mice, had disturbed alignment of BG in the Purkinje cell layer (PCL). We found that Cdc42-KO, but not Rac1-KO, induced impaired radial migration of CGNs in the late phase of radial migration, leading to retention of CGNs in the inferior half of the molecular layer (ML). Cdc42-KO, but not Rac1-KO, mice also showed aberrantly aligned Purkinje cells (PCs). These phenotypes were exacerbated in Cdc42/Rac1-DKO mice. Alignment of BG radial fibers in the ML and BG endfeet at the pial surface of the cerebellum evaluated by GFAP staining was disturbed and weak in Cdc42/Rac1-DKO mice, respectively. Our data indicate that that Cdc42 and Rac, but predominantly Cdc42, in BG play important roles during the late phase of radial migration of CGNs. We also report here that Cdc42 is involved in gliophilic migration of CGNs, in contrast to Rac, which is more closely connected to regulating neurophilic migration.
2018-01-01 | GSE106142 | GEO
Project description:Objectives: We studied the signal transduction of atrial structural remodelling that contributes to the pathogenesis of atrial fibrillation (AF). Backround: Fibrosis is a hallmark of arrhythmogenic structural remodelling but the underlying molecular mechanisms are incompletely understood. Methods: We performed transcriptional profiling of left atrial myocardium (LA) from patients with AF and sinus rhythm (SR) and applied cultured primary cardiac cells and transgenic mice with overexpression of constitutively active V12Rac1 (RacET) who develop AF at old age to characterize mediators of the signal transduction of atrial remodeling. Results: LA from patients with AF showed a marked upregulation of connective tissue growth factor (CTGF) expression compared SR patients. This was associated with increased fibrosis, NADPH-oxidase-, Rac1- and RhoA activity, upregulation of N-cadherin and connexin 43 (Cx43) expression and increased angiotensin II tissue concentration. In neonatal rat cardiac myocytes and -fibroblasts, a specific small molecule inhibitor of Rac1 or simvastatin completely prevented the angiotensin II induced upregulation of CTGF, Cx43 and N-cadherin expression. Transfection with small-inhibiting CTGF RNA blocked Cx43 and N-cadherin expression. RacET mice showed upregulation of CTGF, Cx43 and N-cadherin protein expression. Inhibition of Rac1 by oral statin treatment prevented these effects, identifying Rac1 as a key regulator of CTGF in vivo. Conclusion: The data identify CTGF as an important mediator of atrial structural remodelling during AF. Angiotensin II activates CTGF via activation of Rac1 and NADPH oxidase, leading to upregulation of Cx43, N-cadherin and interstitial fibrosis and therefore contributing to the signal transduction of atrial structural remodelling.
2010-02-11 | GSE14975 | GEO
Project description:The Cdc42/Rac1 regulator CdGAP is a novel E-cadherin transcriptional co-repressor with Zeb2 in breast cancer
| PRJNA341381 | ENA