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