Glutamine metabolism controls amphiregulin-facilitated chemoresistance to cisplatin in human chondrosarcoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1001376 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25496324_1.fastq.gz | Fastqsanger.gz | |||
| SRR25496324_2.fastq.gz | Fastqsanger.gz | |||
| SRR25496325_1.fastq.gz | Fastqsanger.gz | |||
| SRR25496325_2.fastq.gz | Fastqsanger.gz |
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Project description:Chondrosarcoma is the second most common type of bone cancer. At present, the most effective clinical course of action is surgical resection. Cisplatin is the chemotherapeutic medication most widely used for the treatment of chondrosarcoma; however, its effectiveness is severely hampered by drug resistance. In the current study, we compared cisplatin-resistant chondrosarcoma SW1353 cells with their parental cells via RNA sequencing. Our analysis revealed that glutamine metabolism is highly activated in resistant cells but glucose metabolism is not. Amphiregulin (AR), a ligand of the epidermal growth factor receptor, enhances glutamine metabolism and supports cisplatin resistance in human chondrosarcoma by promoting NADPH production and inhibiting ROS accumulation. The MEK, ERK, and NrF2 signaling pathways were shown to regulate AR-mediated SLC1A5 and GLS expression as well as glutamine metabolism in cisplatin-resistant chondrosarcoma. The knockdown of AR expression in cisplatin-resistant chondrosarcoma cells was shown to reduce the expression of SLC1A5 and GLS in vivo. These results indicate that AR and glutamine metabolism are worth pursuing as therapeutic targets in dealing with cisplatin-resistant human chondrosarcoma.
2023-08-07 | GSE239911 | GEO
Project description:Chondrosarcoma is the second most common type of bone cancer. At present, the most effective clinical course of action is surgical resection. Cisplatin is the chemotherapeutic medication most widely used for the treatment of chondrosarcoma; however, its effectiveness is severely hampered by drug resistance. In the current study, we compared cisplatin-resistant chondrosarcoma SW1353 cells with their parental cells via RNA sequencing. Our analysis revealed that glutamine metabolism is highly activated in resistant cells but glucose metabolism is not. Amphiregulin (AR), a ligand of the epidermal growth factor receptor, enhances glutamine metabolism and supports cisplatin resistance in human chondrosarcoma by promoting NADPH production and inhibiting reactive oxygen species (ROS) accumulation. The MEK, ERK, and NrF2 signaling pathways were shown to regulate AR-mediated alanine-serine-cysteine transporter 2 (ASCT2; also called SLC1A5) and glutaminase (GLS) expression as well as glutamine metabolism in cisplatin-resistant chondrosarcoma. The knockdown of AR expression in cisplatin-resistant chondrosarcoma cells was shown to reduce the expression of SLC1A5 and GLS in vivo. These results indicate that AR and glutamine metabolism are worth pursuing as therapeutic targets in dealing with cisplatin-resistant human chondrosarcoma.
| S-EPMC10620823 | biostudies-literature
Project description:Chondrosarcomas are well known for their resistance to chemotherapeutic agents, including cisplatin, which is commonly used in chondrosarcomas. Amphiregulin (AR), a ligand of epidermal growth factor receptor (EGFR), plays an important role in drug resistance. We therefore sought to determine the role of AR in cisplatin chemoresistance. We found that AR inhibits cisplatin-induced cell apoptosis and promotes ATP-binding cassette subfamily B member 1 (ABCB1) expression, while knockdown of ABCB1 by small interfering RNA (siRNA) reverses these effects. High phosphoinositide 3-kinase (PI3K), Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) phosphorylation levels were observed in cisplatin-resistant cells. Pretreating chondrosarcoma cells with PI3K, Akt and NF-κB inhibitors or transfecting the cells with p85, Akt and p65 siRNAs potentiated cisplatin-induced cytotoxicity. In a mouse xenograft model, knockdown of AR expression in chondrosarcoma cells increased the cytotoxic effects of cisplatin and also decreased tumor volume and weight. These results indicate that AR upregulates ABCB1 expression through the PI3K/Akt/NF-κB signaling pathway and thus contributes to cisplatin resistance in chondrosarcoma.
| S-EPMC7288968 | biostudies-literature
Project description:Transcriptional profiling of transgenic mice specifically expressing amphiregulin in white adipose tissues. The objective of this study is to explore gene expression profiles of adipose tissues in response to amphiregulin overexpression.
2017-09-15 | GSE103875 | GEO
Project description:Transcriptional profiling of human chondrosarcoma sphere vs adherent cells
2015-04-30 | GSE47823 | GEO
Project description:These libraries represent instances of Swarm rat chondrosarcoma tumors taken from different transplantation experiments. This series also contains one non-cancerous cartilage library made from rat normal growing femoral head cartilage as a comparative data point. Keywords: other
2004-07-24 | GSE1517 | GEO
Project description:The puropose of this experiment was to identify gene expression changes that result from 5-aza-2-deoxycytidine induced DNA demethylation of Swarm rat chondrosarcoma cells. The gene expression profiles of untreated Swarm rat chondrosarcoma cells were compared to the gene expression profiles of Swarm rat chondrosarcoma cells that were treated for 5 passages with a low dose of 5-aza-2-deoxycytidine (0.1uM).
2010-08-06 | GSE17598 | GEO
Project description:These libraries represent instances of Swarm rat chondrosarcoma tumors taken from different transplantation experiments. This series also contains one non-cancerous cartilage library made from rat normal growing femoral head cartilage as a comparative data point. Keywords: other
2004-07-24 | E-GEOD-1517 | biostudies-arrayexpress
Project description:Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly specify somatic cell fates in cells such as pancreatic ? cells, contractile cardiomyocytes and neurons. We hypothesized that combinatorial expression of chondrocyte-specific transcription factors could directly convert human amnion cells into chondrosarcoma. Starting from a pool of candidate genes, we identified a combination of only five genes (5F pool), BCL6, T (also called BRACHYURY), c-MYC, MITF and BAF60C (also called SMARCD3) that rapidly and efficiently convert postnatal human amnion into chondrosarcoma. The cells generated expressed multiple cartilage-specific genes such as collagen type II ?1, link protein-1 and aggrecan, and exhibited characteristics of cartilage both in vivo and in vitro. Expression of the endogenous genes for T and MITF was initiated, implying that the cell conversion is due to not only the forced expression of the transgenes, but also the cellular reprogramming by the transgenes. The same set of genes converted human placental artery-derived endothelial (hPAE) cells and menstrual blood-derived cells into chondrosarcoma cells, implying that this conversion is independent of cell types. Direct conversion system from non-cartilage tissue to cartilaginous tissue contributes substantially to a major advance toward cartilage development, oncogenesis of chondrocytes, and cell-based therapy. We hypothesized that combinatorial expression of chondrocyte-specific transcription factors could directly convert human amnion cells into chondrosarcoma. Starting from a pool of candidate genes, we identified a combination of only five genes that rapidly efficiently convert postnatal human amnion into chondrosarcoma.
2011-06-07 | E-GEOD-29745 | biostudies-arrayexpress
Project description:The puropose of this experiment was to identify gene expression changes that result from 5-aza-2-deoxycytidine induced DNA demethylation of Swarm rat chondrosarcoma cells. The gene expression profiles of untreated Swarm rat chondrosarcoma cells were compared to the gene expression profiles of Swarm rat chondrosarcoma cells that were treated for 5 passages with a low dose of 5-aza-2-deoxycytidine (0.1uM). Five chip study. For these experiments, microarray was carried out on untreated (control) Swarm rat chondrosarcoma cells (3 biological replicates), and microarray was also carried out on Swarm rat chondrosarcoma cells treated with 5-aza-2-deoxycytidine (2 biological replicates).
2010-08-06 | E-GEOD-17598 | biostudies-arrayexpress