13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression.
13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression.
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DOI：
10.1016/j.cmet.2011.04.012
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发表时间：
2011-07-06
期刊：
影响因子：
29
通讯作者：
Goga A
中科院分区：
文献类型：
--
作者：
Hu S;Balakrishnan A;Bok RA;Anderton B;Larson PE;Nelson SJ;Kurhanewicz J;Vigneron DB;Goga A
肿瘤细胞具有改变的代谢表型，其特征是糖酵解增加和氧化磷酸化减少。尽管人们怀疑糖酵解在肿瘤发生中的重要性，但对癌基因信号传导、体内肿瘤形成和糖酵解途径活性之间的时间关系知之甚少。此外，随着肿瘤消退，糖酵解途径如何改变仍然未知。在这里，我们使用 MYC 驱动的肝癌的可切换模型以及超极化 13C-丙酮酸磁共振波谱成像 (MRSI) 来可视化肿瘤从头形成和消退中的糖酵解。肿瘤中的 LDHA 丰度和活性与体内丙酮酸转化为乳酸密切相关，并且随着肿瘤开始消退而迅速受到抑制，许多糖酵解途径基因也是如此。在可观察到的形态学或组织学变化之前，癌前组织中丙酮酸向丙氨酸的转化占主导地位。这些结果表明代谢变化先于肿瘤形成和消退，并且与单个癌基因的活性直接相关。
Tumor cells have an altered metabolic phenotype characterized by increased glycolysis and diminished oxidative phosphorylation. Despite the suspected importance of glycolysis in tumorigenesis, the temporal relationship between oncogene signaling, in vivo tumor formation and glycolytic pathway activity is poorly understood. Moreover, how glycolytic pathways are altered as tumors regress remains unknown. Here we use a switchable model of MYC-driven liver cancer, along with hyperpolarized 13C-pyruvate magnetic resonance spectroscopic imaging (MRSI) to visualize glycolysis in de novo tumor formation and regression. LDHA abundance and activity in tumors is tightly correlated to in vivo pyruvate conversion to lactate and is rapidly inhibited as tumors begin to regress, as are numerous glycolysis pathway genes. Conversion of pyruvate to alanine predominates in pre-cancerous tissues prior to observable morphologic or histological changes. These results demonstrate that metabolic changes precede tumor formation and regression and are directly linked to the activity of a single oncogene.
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影响因子：
11.2
作者：
Dang CV
通讯作者：
Dang CV
影响因子：
6.2
作者：
HEYMSFIELD, SB;MCMANUS, CB
通讯作者：
MCMANUS, CB
影响因子：
7.3
作者：
Dang, Chi V.
通讯作者：
Dang, Chi V.
影响因子：
82.9
作者：
Goga, Andrei;Yang, Dun;Bishop, J. Michael
通讯作者：
Bishop, J. Michael
影响因子：
3.3
作者：
Hu, Simon;Lustig, Michael;Balakrishnan, Asha;Larson, Peder E. Z.;Bok, Robert;Kurhanewicz, John;Nelson, Sarah J.;Goga, Andrei;Pauly, John M.;Vigneron, Daniel B.
通讯作者：
Vigneron, Daniel B.