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丝氨酸羟甲基转移酶2（SHMT2）通过表观遗传肿瘤抑制因子沉默引发淋巴瘤发展。

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

作者信息

Parsa Sara, Ortega-Molina Ana, Ying Hsia-Yuan, Jiang Man, Teater Matt, Wang Jiahui, Zhao Chunying, Reznik Ed, Pasion Joyce P, Kuo David, Mohan Prathibha, Wang Shenqiu, Camarillo Jeannie M, Thomas Paul M, Jain Neeraj, Garcia-Bermudez Javier, Cho Byoung-Kyu, Tam Wayne, Kelleher Neil L, Socci Nicholas, Dogan Ahmet, De Stanchina Elisa, Ciriello Giovanni, Green Michael R, Li Sheng, Birsoy Kivanc, Melnick Ari M, Wendel Hans-Guido

机构信息

Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Department of Medicine and Weill Cornell Cancer Center, Weill Cornell Medicine, New York, NY, USA.

出版信息

Nat Cancer. 2020;1:653-664. doi: 10.1038/s43018-020-0080-0. Epub 2020 Jun 22.

DOI:10.1038/s43018-020-0080-0
PMID:33569544
原文链接:
https://pmc.ncbi.nlm.nih.gov/articles/PMC7872152/
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. localizes to the most frequent region of copy number gains at chromosome 12q14.1 in lymphoma. Elevated expression of cooperates with in lymphoma development; loss or inhibition of 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 -adenosyl methionine synthesis. SHMT2 induces changes in DNA and histone methylation patterns leading to promoter silencing of previously uncharacterized mutational genes, such as and Together, our findings reveal that amplification of in cooperation with is sufficient in the initiation of lymphomagenesis through epigenetic tumor suppressor silencing.

摘要

癌细胞会调整其代谢活动以支持生长和增殖。然而，代谢酶活性的增加通常不被视为恶性过程中的起始事件。在此，我们研究了丝氨酸羟甲基转移酶-2（SHMT2）在淋巴瘤起始过程中的可能作用。它定位于淋巴瘤中12号染色体q14.1拷贝数增加最频繁的区域。SHMT2的高表达在淋巴瘤发展过程中与[此处原文缺失相关内容]协同作用；SHMT2的缺失或抑制会损害淋巴瘤细胞的存活。SHMT2催化丝氨酸向甘氨酸的转化，并产生一个可用于支持S-腺苷甲硫氨酸合成的活性一碳单位。SHMT2会诱导DNA和组蛋白甲基化模式的改变，导致先前未被表征的突变基因（如[此处原文缺失相关内容]和[此处原文缺失相关内容]）的启动子沉默。我们的研究结果共同表明，SHMT2的扩增与[此处原文缺失相关内容]协同作用，足以通过表观遗传肿瘤抑制因子沉默引发淋巴瘤发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/89cffff805d8/nihms-1654928-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/cb0d75894cb9/nihms-1654928-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/e07f59b2d014/nihms-1654928-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/f6bdb8c1b4e1/nihms-1654928-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/cac6a0fc77e8/nihms-1654928-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/d26c7a321ac0/nihms-1654928-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/57cba6fdeff8/nihms-1654928-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/b06933d58650/nihms-1654928-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/8bad87b85327/nihms-1654928-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/89cffff805d8/nihms-1654928-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/cb0d75894cb9/nihms-1654928-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/e07f59b2d014/nihms-1654928-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/f6bdb8c1b4e1/nihms-1654928-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/cac6a0fc77e8/nihms-1654928-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/d26c7a321ac0/nihms-1654928-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/57cba6fdeff8/nihms-1654928-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/b06933d58650/nihms-1654928-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/8bad87b85327/nihms-1654928-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae3e/7872152/89cffff805d8/nihms-1654928-f0007.jpg

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