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

Détails

ID Serval
serval:BIB_69CD135EB662
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing.
Périodique
Nature cancer
Auteur⸱e⸱s
Parsa S., Ortega-Molina A., Ying H.Y., Jiang M., Teater M., Wang J., Zhao C., Reznik E., Pasion J.P., Kuo D., Mohan P., Wang S., Camarillo J.M., Thomas P.M., Jain N., Garcia-Bermudez J., Cho B.K., Tam W., Kelleher N.L., Socci N., Dogan A., De Stanchina E., Ciriello G., Green M.R., Li S., Birsoy K., Melnick A.M., Wendel H.G.
ISSN
2662-1347 (Electronic)
ISSN-L
2662-1347
Statut éditorial
Publié
Date de publication
2020
Peer-reviewed
Oui
Volume
1
Pages
653-664
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
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.
Pubmed
Création de la notice
22/02/2021 9:57
Dernière modification de la notice
07/07/2021 6:36
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