The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing

被引：1
|
作者：
Sara Parsa
Ana Ortega-Molina
Hsia-Yuan Ying
Man Jiang
Matt Teater
Jiahui Wang
Chunying Zhao
Ed Reznik
Joyce P. Pasion
David Kuo
Prathibha Mohan
Shenqiu Wang
Jeannie M. Camarillo
Paul M. Thomas
Neeraj Jain
Javier Garcia-Bermudez
Byoung-kyu Cho
Wayne Tam
Neil L. Kelleher
Nicholas Socci
Ahmet Dogan
Elisa De Stanchina
Giovanni Ciriello
Michael R. Green
Sheng Li
Kivanc Birsoy
Ari M. Melnick
Hans-Guido Wendel
机构：
[1] Memorial Sloan-Kettering Cancer Center,Cancer Biology and Genetics
[2] Weill Cornell Medicine,Department of Medicine and Weill Cornell Cancer Center
[3] The Jackson Laboratory Cancer Center,Department of Epidemiology and Biostatistics
[4] Memorial Sloan-Kettering Cancer Center,Department of Physiology, Biophysics, and Systems Biology
[5] Weill Cornell Graduate School of Medical Sciences,Department of Chemistry
[6] Molecular Biosciences and the National Resource for Translational and Developmental Proteomics,Department of Lymphoma and Myeloma
[7] Northwestern University,Department of Genomic Medicine
[8] University of Texas MD Anderson Cancer Center,Laboratory of Metabolic Regulation and Genetics
[9] University of Texas MD Anderson Cancer Center,Department of Pathology and Laboratory Medicine
[10] Rockefeller University,Hematopathology Service, Departments of Pathology and Laboratory Medicine
[11] Weill Cornell Medicine,Department of Computational Biology
[12] Memorial Sloan-Kettering Cancer Center,undefined
[13] University of Lausanne,undefined
[14] Swiss Institute of Bioinformatics,undefined
来源：
Nature Cancer | 2020年 / 1卷
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摘要：
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.
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页码：653 / 664
页数：11
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