Energy metabolism during anchorage-independence. Induction by osteopontin-c.
Energy metabolism during anchorage-independence. Induction by osteopontin-c.
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DOI：
10.1371/journal.pone.0105675
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Weber GF
中科院分区：
文献类型：
--
作者：
Shi Z;Wang B;Chihanga T;Kennedy MA;Weber GF
脱落的上皮细胞，但不是癌细胞，导致失巢凋亡由于减少的能量产生。侵袭性肿瘤细胞产生转移基因骨桥蛋白的三种剪接变体，其中最短的（骨桥蛋白-c）支持锚定独立性。骨桥蛋白-c信号上调能量代谢的三个相互依赖的途径。谷胱甘肽、谷氨酰胺和谷氨酸支持一磷酸己糖分流和糖酵解，并可以进入三羧酸循环，导致线粒体ATP的产生。磷酸甘油穿梭的激活也支持线粒体呼吸链。从谷氨酰胺和糖酵解中提取底物，升高的肌酸可以通过甘氨酸从丝氨酸合成，并通过增加ATP的形成来支持能量代谢。用N-乙酰基-L-半胱氨酸、L-谷氨酸或甘油进行的代谢探测确定了途径组分的差异调节，线粒体活性依赖于氧化还原，肌酸途径依赖于谷氨酰胺。细胞代谢中的多个偏斜成分协同作用，通过肌酸和呼吸链流向两种ATP生成机制。这与支持抗失巢凋亡的能量代谢的刺激一致。我们的发现暗示了骨桥蛋白-a和骨桥蛋白-c在癌细胞中的结合，骨桥蛋白-a增加细胞葡萄糖水平，骨桥蛋白-c利用葡萄糖产生能量。
The detachment of epithelial cells, but not cancer cells, causes anoikis due to reduced energy production. Invasive tumor cells generate three splice variants of the metastasis gene osteopontin, the shortest of which (osteopontin-c) supports anchorage-independence. Osteopontin-c signaling upregulates three interdependent pathways of the energy metabolism. Glutathione, glutamine and glutamate support the hexose monophosphate shunt and glycolysis and can feed into the tricarboxylic acid cycle, leading to mitochondrial ATP production. Activation of the glycerol phosphate shuttle also supports the mitochondrial respiratory chain. Drawing substrates from glutamine and glycolysis, the elevated creatine may be synthesized from serine via glycine and supports the energy metabolism by increasing the formation of ATP. Metabolic probing with N-acetyl-L-cysteine, L-glutamate, or glycerol identified differential regulation of the pathway components, with mitochondrial activity being redox dependent and the creatine pathway depending on glutamine. The multiple skewed components in the cellular metabolism synergize in a flow toward two mechanisms of ATP generation, via creatine and the respiratory chain. It is consistent with a stimulation of the energy metabolism that supports anti-anoikis. Our findings imply a coalescence in cancer cells between osteopontin-a, which increases the cellular glucose levels, and osteopontin-c, which utilizes this glucose to generate energy.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1007/978-1-4614-6093-0_1
发表时间：
2013-01-01
期刊：
TAURINE 8, VOL 2: NUTRITION AND METABOLISM, PROTECTIVE ROLE, AND ROLE IN REPRODUCTION, DEVELOPMENT, AND DIFFERENTIATION
影响因子：
--
作者：
Hansen, Svend Hoime;Grunnet, Niels
通讯作者：
Grunnet, Niels
影响因子：
11.2
作者：
Connor, Kip M.;Hempel, Nadine;Melendez, J. Andres
通讯作者：
Melendez, J. Andres
影响因子：
2.9
作者：
Goodpaster, Aaron M.;Romick-Rosendale, Lindsey E.;Kennedy, Michael A.
通讯作者：
Kennedy, Michael A.
影响因子：
64.8
作者：
Possemato, Richard;Marks, Kevin M.;Shaul, Yoav D.;Pacold, Michael E.;Kim, Dohoon;Birsoy, Kivanc;Sethumadhavan, Shalini;Woo, Hin-Koon;Jang, Hyun G.;Jha, Abhishek K.;Chen, Walter W.;Barrett, Francesca G.;Stransky, Nicolas;Tsun, Zhi-Yang;Cowley, Glenn S.;Barretina, Jordi;Kalaany, Nada Y.;Hsu, Peggy P.;Ottina, Kathleen;Chan, Albert M.;Yuan, Bingbing;Garraway, Levi A.;Root, David E.;Mino-Kenudson, Mari;Brachtel, Elena F.;Driggers, Edward M.;Sabatini, David M.
通讯作者：
Sabatini, David M.