Metabolic plasticity of IDH1-mutant glioma cell lines is responsible for low sensitivity to glutaminase inhibition
Background: Targeting glutamine metabolism in cancer has become an increasingly vibrant area of research. Mutant IDH1 (IDH1mut) gliomas are considered good candidates for targeting this pathway because of the contribution of glutamine to their newly acquired function: synthesis of 2-hydroxyglutarate...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
21 October 2020
|
| In: |
Cancer & metabolism
Year: 2020, Jahrgang: 8 |
| ISSN: | 2049-3002 |
| DOI: | 10.1186/s40170-020-00229-2 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1186/s40170-020-00229-2
|
| Verfasserangaben: | Victor Ruiz-Rodado, Adrian Lita, Tyrone Dowdy, Orieta Celiku, Alejandra Cavazos Saldana, Herui Wang, Chun Zhang Yang, Raj Chari, Aiguo Li, Wei Zhang, Hua Song, Meili Zhang, Susie Ahn, Dionne Davis, Xiang Chen, Zhengping Zhuang, Christel Herold-Mende, Kylie J. Walters, Mark R. Gilbert and Mioara Larion |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1740775767 | ||
| 003 | DE-627 | ||
| 005 | 20220819032639.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 201124s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s40170-020-00229-2 |2 doi | |
| 035 | |a (DE-627)1740775767 | ||
| 035 | |a (DE-599)KXP1740775767 | ||
| 035 | |a (OCoLC)1341377927 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Ruiz-Rodado, Victor |e VerfasserIn |0 (DE-588)1207793760 |0 (DE-627)1694137961 |4 aut | |
| 245 | 1 | 0 | |a Metabolic plasticity of IDH1-mutant glioma cell lines is responsible for low sensitivity to glutaminase inhibition |c Victor Ruiz-Rodado, Adrian Lita, Tyrone Dowdy, Orieta Celiku, Alejandra Cavazos Saldana, Herui Wang, Chun Zhang Yang, Raj Chari, Aiguo Li, Wei Zhang, Hua Song, Meili Zhang, Susie Ahn, Dionne Davis, Xiang Chen, Zhengping Zhuang, Christel Herold-Mende, Kylie J. Walters, Mark R. Gilbert and Mioara Larion |
| 264 | 1 | |c 21 October 2020 | |
| 300 | |a 14 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 24.11.2020 | ||
| 520 | |a Background: Targeting glutamine metabolism in cancer has become an increasingly vibrant area of research. Mutant IDH1 (IDH1mut) gliomas are considered good candidates for targeting this pathway because of the contribution of glutamine to their newly acquired function: synthesis of 2-hydroxyglutarate (2HG). Methods: We have employed a combination of 13C tracers including glutamine and glucose for investigating the metabolism of patient-derived IDH1mut glioma cell lines through NMR and LC/MS. Additionally, genetic loss-of-function (in vitro and in vivo) approaches were performed to unravel the adaptability of these cell lines to the inhibition of glutaminase activity. Results: We report the adaptability of IDH1mut cells’ metabolism to the inhibition of glutamine/glutamate pathway. The glutaminase inhibitor CB839 generated a decrease in the production of the downstream metabolites of glutamate, including those involved in the TCA cycle and 2HG. However, this effect on metabolism was not extended to viability; rather, our patient-derived IDH1mut cell lines display a metabolic plasticity that allows them to overcome glutaminase inhibition. Conclusions: Major metabolic adaptations involved pathways that can generate glutamate by using alternative substrates from glutamine, such as alanine or aspartate. Indeed, asparagine synthetase was upregulated both in vivo and in vitro revealing a new potential therapeutic target for a combinatory approach with CB839 against IDH1mut gliomas. | ||
| 700 | 1 | |a Lita, Adrian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dowdy, Tyrone |e VerfasserIn |4 aut | |
| 700 | 1 | |a Celiku, Orieta |e VerfasserIn |4 aut | |
| 700 | 1 | |a Saldana, Alejandra Cavazos |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wang, Herui |e VerfasserIn |4 aut | |
| 700 | 1 | |a Yang, Chun Zhang |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chari, Raj |e VerfasserIn |4 aut | |
| 700 | 1 | |a Li, Aiguo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zhang, Wei |e VerfasserIn |4 aut | |
| 700 | 1 | |a Song, Hua |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zhang, Meili |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ahn, Susie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Davis, Dionne |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chen, Xiang |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zhuang, Zhengping |e VerfasserIn |4 aut | |
| 700 | 1 | |a Herold-Mende, Christel |e VerfasserIn |0 (DE-588)1022936549 |0 (DE-627)717335577 |0 (DE-576)366194267 |4 aut | |
| 700 | 1 | |a Walters, Kylie J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gilbert, Mark R. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Larion, Mioara |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cancer & metabolism |d London : Biomed Central, 2013 |g 8(2020) Artikel-Nummer 23, 14 Seiten |h Online-Ressource |w (DE-627)735134936 |w (DE-600)2700141-6 |w (DE-576)378186884 |x 2049-3002 |7 nnas |a Metabolic plasticity of IDH1-mutant glioma cell lines is responsible for low sensitivity to glutaminase inhibition |
| 773 | 1 | 8 | |g volume:8 |g year:2020 |g extent:14 |a Metabolic plasticity of IDH1-mutant glioma cell lines is responsible for low sensitivity to glutaminase inhibition |
| 856 | 4 | 0 | |u https://doi.org/10.1186/s40170-020-00229-2 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20201124 | ||
| 993 | |a Article | ||
| 994 | |a 2020 | ||
| 998 | |g 1022936549 |a Herold-Mende, Christel |m 1022936549:Herold-Mende, Christel |d 910000 |d 911200 |e 910000PH1022936549 |e 911200PH1022936549 |k 0/910000/ |k 1/910000/911200/ |p 17 | ||
| 999 | |a KXP-PPN1740775767 |e 3811633864 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"type":{"bibl":"article-journal","media":"Online-Ressource"},"recId":"1740775767","id":{"doi":["10.1186/s40170-020-00229-2"],"eki":["1740775767"]},"origin":[{"dateIssuedDisp":"21 October 2020","dateIssuedKey":"2020"}],"name":{"displayForm":["Victor Ruiz-Rodado, Adrian Lita, Tyrone Dowdy, Orieta Celiku, Alejandra Cavazos Saldana, Herui Wang, Chun Zhang Yang, Raj Chari, Aiguo Li, Wei Zhang, Hua Song, Meili Zhang, Susie Ahn, Dionne Davis, Xiang Chen, Zhengping Zhuang, Christel Herold-Mende, Kylie J. Walters, Mark R. Gilbert and Mioara Larion"]},"language":["eng"],"note":["Gesehen am 24.11.2020"],"person":[{"display":"Ruiz-Rodado, Victor","family":"Ruiz-Rodado","role":"aut","given":"Victor"},{"given":"Adrian","role":"aut","family":"Lita","display":"Lita, Adrian"},{"role":"aut","family":"Dowdy","display":"Dowdy, Tyrone","given":"Tyrone"},{"given":"Orieta","role":"aut","family":"Celiku","display":"Celiku, Orieta"},{"family":"Saldana","role":"aut","display":"Saldana, Alejandra Cavazos","given":"Alejandra Cavazos"},{"family":"Wang","role":"aut","display":"Wang, Herui","given":"Herui"},{"role":"aut","family":"Yang","display":"Yang, Chun Zhang","given":"Chun Zhang"},{"given":"Raj","family":"Chari","role":"aut","display":"Chari, Raj"},{"display":"Li, Aiguo","family":"Li","role":"aut","given":"Aiguo"},{"given":"Wei","display":"Zhang, Wei","role":"aut","family":"Zhang"},{"given":"Hua","display":"Song, Hua","role":"aut","family":"Song"},{"display":"Zhang, Meili","role":"aut","family":"Zhang","given":"Meili"},{"family":"Ahn","role":"aut","display":"Ahn, Susie","given":"Susie"},{"given":"Dionne","display":"Davis, Dionne","role":"aut","family":"Davis"},{"family":"Chen","role":"aut","display":"Chen, Xiang","given":"Xiang"},{"role":"aut","family":"Zhuang","display":"Zhuang, Zhengping","given":"Zhengping"},{"given":"Christel","display":"Herold-Mende, Christel","role":"aut","family":"Herold-Mende"},{"display":"Walters, Kylie J.","family":"Walters","role":"aut","given":"Kylie J."},{"family":"Gilbert","role":"aut","display":"Gilbert, Mark R.","given":"Mark R."},{"given":"Mioara","role":"aut","family":"Larion","display":"Larion, Mioara"}],"relHost":[{"id":{"eki":["735134936"],"zdb":["2700141-6"],"issn":["2049-3002"]},"recId":"735134936","type":{"bibl":"periodical","media":"Online-Ressource"},"disp":"Metabolic plasticity of IDH1-mutant glioma cell lines is responsible for low sensitivity to glutaminase inhibitionCancer & metabolism","origin":[{"dateIssuedDisp":"2013-","publisherPlace":"London","dateIssuedKey":"2013","publisher":"Biomed Central"}],"note":["Gesehen am 25.01.13"],"pubHistory":["1.2013 -"],"language":["eng"],"part":{"extent":"14","volume":"8","year":"2020","text":"8(2020) Artikel-Nummer 23, 14 Seiten"},"physDesc":[{"extent":"Online-Ressource"}],"title":[{"title_sort":"Cancer & metabolism","title":"Cancer & metabolism"}]}],"title":[{"title":"Metabolic plasticity of IDH1-mutant glioma cell lines is responsible for low sensitivity to glutaminase inhibition","title_sort":"Metabolic plasticity of IDH1-mutant glioma cell lines is responsible for low sensitivity to glutaminase inhibition"}],"physDesc":[{"extent":"14 S."}]} | ||
| SRT | |a RUIZRODADOMETABOLICP2120 | ||