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BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1

Title
BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1
Authors
Tonjes M.Barbus S.Park Y.J.Wang W.Schlotter M.Lindroth A.M.Pleier S.V.Bai A.H.C.Karra D.Piro R.M.Felsberg J.Addington A.Lemke D.Weibrecht I.Hovestadt V.Rolli C.G.Campos B.Turcan S.Sturm D.Witt H.Chan T.A.Herold-Mende C.Kemkemer R.Konig R.Schmidt K.Hull W.-E.Pfister S.M.Jugold M.Hutson S.M.Plass C.Okun J.G.Reifenberger G.Lichter P.Radlwimmer B.
Ewha Authors
박윤정
SCOPUS Author ID
박윤정scopus
Issue Date
2013
Journal Title
Nature Medicine
ISSN
1078-8956JCR Link
Citation
vol. 19, no. 7, pp. 901 - 908
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Here we show that glioblastoma express high levels of branched-chain amino acid transaminase 1 (BCAT1), the enzyme that initiates the catabolism of branched-chain amino acids (BCAAs). Expression of BCAT1 was exclusive to tumors carrying wild-type isocitrate dehydrogenase 1 (IDH1) and IDH2 genes and was highly correlated with methylation patterns in the BCAT1 promoter region. BCAT1 expression was dependent on the concentration of α-ketoglutarate substrate in glioma cell lines and could be suppressed by ectopic overexpression of mutant IDH1 in immortalized human astrocytes, providing a link between IDH1 function and BCAT1 expression. Suppression of BCAT1 in glioma cell lines blocked the excretion of glutamate and led to reduced proliferation and invasiveness in vitro, as well as significant decreases in tumor growth in a glioblastoma xenograft model. These findings suggest a central role for BCAT1 in glioma pathogenesis, making BCAT1 and BCAA metabolism attractive targets for the development of targeted therapeutic approaches to treat patients with glioblastoma.
DOI
10.1038/nm.3217
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신산업융합대학 > 식품영양학과 > Journal papers
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