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- Publisher Website: 10.1016/j.celrep.2021.109617
- Scopus: eid_2-s2.0-85113371667
- PMID: 34433044
- WOS: WOS:000688508300052
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Article: Loss of tyrosine catabolic enzyme HPD promotes glutamine anaplerosis through mTOR signaling in liver cancer
Title | Loss of tyrosine catabolic enzyme HPD promotes glutamine anaplerosis through mTOR signaling in liver cancer |
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Authors | |
Keywords | tyrosine catabolism HPD liver cancer glutamine metabolism mTOR signaling |
Issue Date | 2021 |
Publisher | Elsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports |
Citation | Cell Reports, 2021, v. 36 n. 8, p. article no. 109617 How to Cite? |
Abstract | The liver plays central roles in coordinating different metabolic processes, such as the catabolism of amino acids. In this study, we identify a loss of tyrosine catabolism and a concomitant increase in serum tyrosine levels during liver cancer development. Liver cells with disordered tyrosine catabolism, as exemplified by the suppression of a tyrosine catabolic enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD), display augmented tumorigenic and proliferative potentials. Metabolomics profiling and isotope tracing reveal the metabolic reliance of HPD-silenced cells on glutamine, coupled with increased tricarboxylic acid cycle metabolites and their associated amino acid pools. Mechanistically, HPD silencing reduces ketone bodies, which regulate the proliferative and metabolic phenotypes via the AMPK/mTOR/p70S6 kinase pathway and mTOR-dependent glutaminase (GLS) activation. Collectively, our results demonstrate a metabolic link between tyrosine and glutamine metabolism, which could be exploited as a potentially promising anticancer therapy for liver cancer. |
Persistent Identifier | http://hdl.handle.net/10722/306281 |
ISSN | 2023 Impact Factor: 7.5 2023 SCImago Journal Rankings: 4.279 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Tong, M | - |
dc.contributor.author | Wong, TL | - |
dc.contributor.author | Zhao, H | - |
dc.contributor.author | Zheng, Y | - |
dc.contributor.author | XIE, YN | - |
dc.contributor.author | Li, CH | - |
dc.contributor.author | Zhou, L | - |
dc.contributor.author | CHE, N | - |
dc.contributor.author | Yun, JP | - |
dc.contributor.author | Man, K | - |
dc.contributor.author | Lee, TKW | - |
dc.contributor.author | Cai, Z | - |
dc.contributor.author | Ma, S | - |
dc.date.accessioned | 2021-10-20T10:21:23Z | - |
dc.date.available | 2021-10-20T10:21:23Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Cell Reports, 2021, v. 36 n. 8, p. article no. 109617 | - |
dc.identifier.issn | 2211-1247 | - |
dc.identifier.uri | http://hdl.handle.net/10722/306281 | - |
dc.description.abstract | The liver plays central roles in coordinating different metabolic processes, such as the catabolism of amino acids. In this study, we identify a loss of tyrosine catabolism and a concomitant increase in serum tyrosine levels during liver cancer development. Liver cells with disordered tyrosine catabolism, as exemplified by the suppression of a tyrosine catabolic enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD), display augmented tumorigenic and proliferative potentials. Metabolomics profiling and isotope tracing reveal the metabolic reliance of HPD-silenced cells on glutamine, coupled with increased tricarboxylic acid cycle metabolites and their associated amino acid pools. Mechanistically, HPD silencing reduces ketone bodies, which regulate the proliferative and metabolic phenotypes via the AMPK/mTOR/p70S6 kinase pathway and mTOR-dependent glutaminase (GLS) activation. Collectively, our results demonstrate a metabolic link between tyrosine and glutamine metabolism, which could be exploited as a potentially promising anticancer therapy for liver cancer. | - |
dc.language | eng | - |
dc.publisher | Elsevier (Cell Press): OAJ. The Journal's web site is located at http://cell.com/cell-reports | - |
dc.relation.ispartof | Cell Reports | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | tyrosine catabolism | - |
dc.subject | HPD | - |
dc.subject | liver cancer | - |
dc.subject | glutamine metabolism | - |
dc.subject | mTOR signaling | - |
dc.title | Loss of tyrosine catabolic enzyme HPD promotes glutamine anaplerosis through mTOR signaling in liver cancer | - |
dc.type | Article | - |
dc.identifier.email | Tong, M: caroltm@hku.hk | - |
dc.identifier.email | Wong, TL: tinlwong@hku.hk | - |
dc.identifier.email | Man, K: kwanman@hku.hk | - |
dc.identifier.email | Ma, S: stefma@hku.hk | - |
dc.identifier.authority | Tong, M=rp02568 | - |
dc.identifier.authority | Wong, TL=rp02845 | - |
dc.identifier.authority | Man, K=rp00417 | - |
dc.identifier.authority | Ma, S=rp00506 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1016/j.celrep.2021.109617 | - |
dc.identifier.pmid | 34433044 | - |
dc.identifier.scopus | eid_2-s2.0-85113371667 | - |
dc.identifier.hkuros | 327650 | - |
dc.identifier.volume | 36 | - |
dc.identifier.issue | 8 | - |
dc.identifier.spage | article no. 109617 | - |
dc.identifier.epage | article no. 109617 | - |
dc.identifier.isi | WOS:000688508300052 | - |
dc.publisher.place | United States | - |