| Literature DB >> 33569544 |
Sara Parsa1, Ana Ortega-Molina1, Hsia-Yuan Ying2, Man Jiang1, Matt Teater2, Jiahui Wang3, Chunying Zhao1, Ed Reznik4, Joyce P Pasion1, David Kuo5, Prathibha Mohan1, Shenqiu Wang1, Jeannie M Camarillo6, Paul M Thomas6, Neeraj Jain7,8, Javier Garcia-Bermudez9, Byoung-Kyu Cho6, Wayne Tam10, Neil L Kelleher6, Nicholas Socci1, Ahmet Dogan11, Elisa De Stanchina1, Giovanni Ciriello12,13, Michael R Green7,8, Sheng Li3, Kivanc Birsoy9, Ari M Melnick2, Hans-Guido Wendel14.
Abstract
Cancer cells adapt their metabolic activities to support growth and proliferation. However, increased activity of metabolic enzymes is not usually considered an initiating event in the malignant process. Here, we investigate the possible role of the enzyme serine hydroxymethyltransferase-2 (SHMT2) in lymphoma initiation. SHMT2 localizes to the most frequent region of copy number gains at chromosome 12q14.1 in lymphoma. Elevated expression of SHMT2 cooperates with BCL2 in lymphoma development; loss or inhibition of SHMT2 impairs lymphoma cell survival. SHMT2 catalyzes the conversion of serine to glycine and produces an activated one-carbon unit that can be used to support S-adenosyl methionine synthesis. SHMT2 induces changes in DNA and histone methylation patterns leading to promoter silencing of previously uncharacterized mutational genes, such as SASH1 and PTPRM. Together, our findings reveal that amplification of SHMT2 in cooperation with BCL2 is sufficient in the initiation of lymphomagenesis through epigenetic tumor suppressor silencing.Entities:
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Year: 2020 PMID： 33569544 PMCID： PMC7872152 DOI： 10.1038/s43018-020-0080-0
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347