Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1099462 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cellular metabolism is an integral component of cellular adaptation to stress, consequently, metabolism plays a pivotal role in the resistance of cancer cells to a range of treatment modalities. Radiotherapy is used to treat approximately half of all cancer patients, however, most are either inherently radioresistant or acquire resistance over time. Effective radiotherapy relies on generating an overwhelming burden of DNA damage which triggers cell death. In response to radiotherapy cancer cells engage antioxidant and DNA repair mechanisms which mitigate and remove DNA damage, facilitating cancer cell survival. Given the reliance of these resistance mechanisms on amino acid metabolism we hypothesised that controlling the availability of the exogenous amino acids serine and glycine would be an effective strategy to radiosensitive cancer cells. Here we show that serine and glycine restriction sensitised a range of cancer cell lines, patient derived organoids and syngeneic mouse tumour models to radiotherapy. Comprehensive metabolomic analysis of central carbon metabolism revealed that amino acid restriction impacted not only glutathione and nucleotide synthesis but had an unexpected impact on the TCA cycle and antagonised a key cellular redox response to radiotherapy mediated by reductive carboxylation.
2022-11-02 | GSE190668 | GEO
Project description:Myeloid amino acid metabolism supports solid tumor malignancy
| PRJNA518914 | ENA
Project description:The objective of this study was to analyze AHR activation through aromatic amino acid metabolism. To this end, glioblastoma cells were exposed to aromatic amino acid derived metabolites and their ability to activate AHR was analysed. In addition, AHR activation was evaluated in glioblastoma cells expressing IL4I1, an aromatic amino acid degrading enzyme, with or without shRNA mediated knockdown of AHR.
2020-08-19 | GSE129977 | GEO
Project description:The objective of this study was to analyze AHR activation through aromatic amino acid metabolism. To this end, glioblastoma cells were exposed to aromatic amino acid derived metabolites and their ability to activate AHR was analysed. In addition, AHR activation was evaluated in glioblastoma cells expressing IL4I1, an aromatic amino acid degrading enzyme, with or without shRNA mediated knockdown of AHR.
2020-08-19 | GSE129976 | GEO
Project description:The objective of this study was to analyze AHR activation through aromatic amino acid metabolism. To this end, glioblastoma cells were exposed to aromatic amino acid derived metabolites and their ability to activate AHR was analysed. In addition, AHR activation was evaluated in glioblastoma cells expressing IL4I1, an aromatic amino acid degrading enzyme, with or without shRNA mediated knockdown of AHR.
2020-08-19 | GSE129974 | GEO
Project description:The objective of this study was to analyze AHR activation through aromatic amino acid metabolism. To this end, glioblastoma cells were exposed to aromatic amino acid derived metabolites and their ability to activate AHR was analysed. In addition, AHR activation was evaluated in glioblastoma cells expressing IL4I1, an aromatic amino acid degrading enzyme, with or without shRNA mediated knockdown of AHR.
2020-08-19 | GSE129972 | GEO
Project description:Proliferating tumor cells use aerobic glycolysis to support their high metabolic demands. Paradoxically, increased glycolysis is often accompanied by expression of the lower activity PKM isoform, effectively constraining lower glycolysis. Here, we report the discovery of novel PKM activators with a unique allosteric binding mode. Characterization of how these compounds impact cancer cells revealed an unanticipated link between glucose and amino acid metabolism. PKM activation resulted in a metabolic rewiring of cancer cells manifested by a profound dependency on the non-essential amino acid serine for continued cell proliferation. Induction of serine auxotrophy by PKM activation was accompanied by reduced carbon flow into the serine biosynthetic pathway and increased expression of high affinity serine transporters. These data support the hypothesis that PKM expression confers metabolic flexibility to cancer cells that allows adaptation to nutrient stress. A549 cancer cells were treated with compound-16 for up to 24 hours in the presence and absence of serine in the media.
2012-12-20 | E-GEOD-40191 | biostudies-arrayexpress
Project description:Identification of genes involved in aromatic amino acid metabolism
| PRJNA290001 | ENA