Glutamine depletion regulates Slug to promote EMT and metastasis in pancreatic cancer
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ABSTRACT:
PROVIDER: PRJNA633897 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11813358.fastq.gz | Fastqsanger.gz | |||
| SRR11813359.fastq.gz | Fastqsanger.gz | |||
| SRR11813360.fastq.gz | Fastqsanger.gz | |||
| SRR11813361.fastq.gz | Fastqsanger.gz | |||
| SRR11813362.fastq.gz | Fastqsanger.gz |
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Project description:Tumor cells rely on glutamine to fulfill their metabolic demands and sustain proliferation. The elevated consumption of glutamine can lead to intratumoral nutrient depletion, causing metabolic stress that has the potential to impact tumor progression. Here, we show that nutrient stress caused by glutamine deprivation leads to the induction of epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) cells. Mechanistically, we demonstrate that glutamine deficiency regulates EMT through the upregulation of the EMT master regulator Slug, a process that is dependent on both MEK/ERK signaling and ATF4. We find that Slug is required in PDAC cells for glutamine deprivation-induced EMT, cell motility and nutrient stress survival. Importantly, we decipher that Slug is associated with nutrient stress in PDAC tumors and is required for metastasis. These results delineate a novel role for Slug in the nutrient stress response and provide insight into how nutrient depletion might influence PDAC progression.
2020-05-20 | GSE150874 | GEO
Project description:Tumor cells rely on glutamine to fulfill their metabolic demands and sustain proliferation. The elevated consumption of glutamine can lead to intratumoral nutrient depletion, causing metabolic stress that has the potential to impact tumor progression. Here, we show that nutrient stress caused by glutamine deprivation leads to the induction of epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) cells. Mechanistically, we demonstrate that glutamine deficiency regulates EMT through the upregulation of the EMT master regulator Slug, a process that is dependent on both MEK/ERK signaling and ATF4. We find that Slug is required in PDAC cells for glutamine deprivation-induced EMT, cell motility and nutrient stress survival. Importantly, we decipher that Slug is associated with nutrient stress in PDAC tumors and is required for metastasis. These results delineate a novel role for Slug in the nutrient stress response and provide insight into how nutrient depletion might influence PDAC progression.
2020-05-20 | GSE150873 | GEO
Project description:Glutamine depletion regulates Slug to promote EMT and metastasis in pancreatic cancer [human]
| PRJNA633899 | ENA
Project description:Glutamine depletion regulates Slug to promote EMT and metastasis in pancreatic cancer [mouse]
| PRJNA633900 | ENA
Project description:Tumor cells rely on glutamine to fulfill their metabolic demands and sustain proliferation. The elevated consumption of glutamine can lead to intratumoral nutrient depletion, causing metabolic stress that has the potential to impact tumor progression. Here, we show that nutrient stress caused by glutamine deprivation leads to the induction of epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) cells. Mechanistically, we demonstrate that glutamine deficiency regulates EMT through the up-regulation of the EMT master regulator Slug, a process that is dependent on both MEK/ERK signaling and ATF4. We find that Slug is required in PDAC cells for glutamine deprivation-induced EMT, cell motility, and nutrient stress survival. Importantly, we decipher that Slug is associated with nutrient stress in PDAC tumors and is required for metastasis. These results delineate a novel role for Slug in the nutrient stress response and provide insight into how nutrient depletion might influence PDAC progression.
| S-EPMC7478719 | biostudies-literature
Project description:Neoadjuvant chemotherapy (NACT) followed by radical surgery for patients in FIGO stages IB2-IIB has proven to reduce tumor volume and numbers. However, NACT followed by radical surgery has not been found to improve overall survival. In this study, 35 paired pre/post-NACT cervical cancer tissues and 167 cervical cancer samples were examined by immunohistochemical analysis, SLUG expression was potentially increased in cervical cancer tissues after neoadjuvant chemotherapy, which in turn positively correlated with pelvic lymph node metastasis. The expression of SLUG following neoadjuvant chemotherapy was identified as a poor survival indicator. Functional assays, Agilent microarray hybridization and CHIP assay were performed to determine SLUG’s downstream genes and pathways. SLUG overexpression promoted metastasis in cervical cancer in both in vitro and in vivo models, whereas SLUG silencing had the opposite effect. Mechanically, SLUG is not a prerequisite for EMT activation in cervical cancer models, but contributes to the invasiveness and metastasis of cervical cancer cells by directly tethering to the recognition sequence GCCAGGTGC in the MMP3 promoter region. Our results provide mechanistic insight into the potential pro-cancer effect of neoadjuvant chemotherapy, and demonstrates that the SLUG-MMP3 axis could serve as a target for improving the efficacy of chemotherapy.
2020-12-11 | GSE163002 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-05-20 | GSE150875 | GEO
Project description:Background: The well-characterized function of the transcriptional repressor, Slug, is to promote EMT and tumor invasion/metastasis by down-regulating E-cadherin expression. In this study, we investigated the significance of Slug during the S phase. Method: Slug mRNA expression was isolated from thymidine-arrested CL1-5/AS2neo (control) and CL1-5/AS2neo-Slug-WT stable cells. The Agilent oligonucleotide microarray analysis was performed to identify Slug downstream genes. Results: Overexpression of Slug inhibited lung [3H]-thymidine incorporation and delayed S phase progression. By using Agilent microarray we have identified panel of genes altered by Slug overexpression. Slug can down-regulate target genes about cell cycle networks for DNA replication, DNA replication checkpoint and genomic stability, such as TOP1, ORC4, RFC3, and Rad17. Conclusions: the multifaceted role of Slug in cancer progression by controlling the epithelial-mesenchymal transition and genome stability.
2012-02-09 | GSE35617 | GEO
Project description:Background: The well-characterized function of the transcriptional repressor, Slug, is to promote EMT and tumor invasion/metastasis by down-regulating E-cadherin expression. In this study, we investigated the significance of Slug during the S phase. Method: Slug mRNA expression was isolated from thymidine-arrested CL1-5/AS2neo (control) and CL1-5/AS2neo-Slug-WT stable cells. The Agilent oligonucleotide microarray analysis was performed to identify Slug downstream genes. Results: Overexpression of Slug inhibited lung [3H]-thymidine incorporation and delayed S phase progression. By using Agilent microarray we have identified panel of genes altered by Slug overexpression. Slug can down-regulate target genes about cell cycle networks for DNA replication, DNA replication checkpoint and genomic stability, such as TOP1, ORC4, RFC3, and Rad17. Conclusions: the multifaceted role of Slug in cancer progression by controlling the epithelial-mesenchymal transition and genome stability. Two-condition experiment, Vector vs. Slug overexpression cells. The cDNAs encoding full-length human Slug were amplified and subcloned into lentiviral pLKO_AS2.neo which generated full-length Slug. Vector control or Slug lentivirus were transduced into CL1-5 cells and Gentamycin was used to select stable cells.
2012-02-09 | E-GEOD-35617 | biostudies-arrayexpress
Project description:The epithelial-mesenchymal transition (EMT) is thought to be essential for cancer metastasis. While chromatin remodeling is involved in EMT, histone variants contribution in EMT remains poorly investigated. Recently, we showed that silencing or removal of the histone variant H2A.X induced mesenchymal-like characteristics, including activation of the EMT transcription factors, Slug and ZEB1, in human colon cancer cells. Here, we provide the evidence that H2A.X loss in human non-tumorigenic breast cell line MCF10A results in a robust EMT activation, as substantiated by a genome-wide expression analysis. Cells deficient for H2A.X exhibit enhanced migration and invasion, along with an activation of a set of mesenchymal genes and a concomitant repression of epithelial genes. In the breast model, the EMT-related transcription factor Twist1 cooperates with Slug to regulate EMT upon H2A.X loss. Of interest, H2A.X expression level tightly correlates with Twist1, and to a lesser extent with Slug in the panel of human breast cancer cell lines of the NCI-60 datasets. These new findings indicate that H2A.X is involved in the EMT processes in cells of different origins but pairing with transcription factors for EMT may be tissue specific.
2016-06-21 | GSE80180 | GEO