Project description:ACSS2-mediated acetylation promotes BCAT1 aggradation to elevate branched-chain amino acid metabolism and development of pancreatic cancer
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.
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.
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.
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.
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.
