Journal
BLOOD CANCER JOURNAL
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bcj.2017.61
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Funding
- National Natural Science Foundation of China [81325003, 81520108003, 81670716, 81201863]
- Shanghai Commission of Science and Technology [14430723400, 14140903100, 16JC1405800]
- National Key Research and Development Program [2016YFC0902800]
- Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant [20152206, 20152208]
- Multi-center Clinical Research Project by Shanghai Jiao Tong University School of Medicine [DLY201601]
- SMC-Chen Xing Scholars Program
- Chang Jiang Scholars Program
- Shanghai Jiao Tong University [BXJ201607]
- Collaborative Innovation Center of Systems Biomedicine
- Samuel Waxman Cancer Research Foundation
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The activation of oncogenes can reprogram tumor cell metabolism. Here, in diffuse large B-cell lymphoma (DLBCL), serum metabolomic analysis revealed that oncogenic MYC could induce aberrant choline metabolism by transcriptionally activating the key enzyme phosphate cytidylyltransferase 1 choline-alpha (PCYT1A). In B-lymphoma cells, as a consequence of PCYT1A upregulation, MYC impeded lymphoma cells undergo a mitophagy-dependent necroptosis. In DLBCL patients, overexpression of PCYT1A was in parallel with an increase in tumor MYC, as well as a decrease in serum choline metabolite phosphatidylcholine levels and an International Prognostic Index, indicating intermediate-high or high risk. Both in vitro and in vivo, lipid-lowering alkaloid berberine (BBR) exhibited an anti-lymphoma activity through inhibiting MYC-driven downstream PCYT1A expression and inducing mitophagy-dependent necroptosis. Collectively, PCYT1A was upregulated by MYC, which resulted in the induction of aberrant choline metabolism and the inhibition of B-lymphoma cell necroptosis. Referred as a biomarker for DLBCL progression, PCYT1A can be targeted by BBR, providing a potential lipid-modifying strategy in treating MYC-High lymphoma.
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