Importance of glycolysis and oxidative phosphorylation in advanced melanoma.
Importance of glycolysis and oxidative phosphorylation in advanced melanoma.
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DOI：
10.1186/1476-4598-11-76
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发表时间：
2012-10-09
期刊：
影响因子：
37.3
通讯作者：
Moschos SJ
中科院分区：
文献类型：
--
作者：
Ho J;de Moura MB;Lin Y;Vincent G;Thorne S;Duncan LM;Hui-Min L;Kirkwood JM;Becker D;Van Houten B;Moschos SJ
血清乳酸脱氢酶（LDH）是IV期黑色素瘤患者的预后因素。为了深入了解这一预后因素的生物学基础，我们分析了多达49例转移性黑色素瘤患者的总血清LDH、血清LDH同工酶和血清乳酸。我们的数据表明，高血清LDH与LDH同工酶3和4的显着增加，LDH同工酶1和2的减少。由于LDH同工酶在糖酵解和氧化磷酸化（OXPHOS）中起作用，我们随后使用组织微阵列（TMA）分析确定，与线粒体功能，乳酸代谢和糖酵解调节剂相关的蛋白质水平在晚期黑色素瘤中均高于痣黑色素细胞。为了研究在晚期黑色素瘤中糖酵解和OXPHOS通路是否可能相关，我们测定了单羧酸转运蛋白（MCT）1和4的表达。对痣至黑色素瘤进展TMA的分析显示，随着进展至晚期黑色素瘤，MCT 4和较小程度的MCT 1升高。使用Seahorse XF24细胞外通量分析仪对人黑素瘤标本的进一步分析表明，转移性黑素瘤肿瘤从OXPHOS获得大部分能量。两者合计，这些发现表明，在IV期黑色素瘤与正常血清LDH，糖酵解和OXPHOS可能提供代谢共生在同一肿瘤内，而在IV期黑色素瘤与高血清LDH糖酵解是能量的主要来源。
Serum lactate dehydrogenase (LDH) is a prognostic factor for patients with stage IV melanoma. To gain insights into the biology underlying this prognostic factor, we analyzed total serum LDH, serum LDH isoenzymes, and serum lactate in up to 49 patients with metastatic melanoma. Our data demonstrate that high serum LDH is associated with a significant increase in LDH isoenzymes 3 and 4, and a decrease in LDH isoenzymes 1 and 2. Since LDH isoenzymes play a role in both glycolysis and oxidative phosphorylation (OXPHOS), we subsequently determined using tissue microarray (TMA) analysis that the levels of proteins associated with mitochondrial function, lactate metabolism, and regulators of glycolysis were all elevated in advanced melanomas compared with nevic melanocytes. To investigate whether in advanced melanoma, the glycolysis and OXPHOS pathways might be linked, we determined expression of the monocarboxylate transporters (MCT) 1 and 4. Analysis of a nevus-to-melanoma progression TMA revealed that MCT4, and to a lesser extend MCT1, were elevated with progression to advanced melanoma. Further analysis of human melanoma specimens using the Seahorse XF24 extracellular flux analyzer indicated that metastatic melanoma tumors derived a large fraction of energy from OXPHOS. Taken together, these findings suggest that in stage IV melanomas with normal serum LDH, glycolysis and OXPHOS may provide metabolic symbiosis within the same tumor, whereas in stage IV melanomas with high serum LDH glycolysis is the principle source of energy.
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影响因子：
5.6
作者：
Porporato PE;Dhup S;Dadhich RK;Copetti T;Sonveaux P
通讯作者：
Sonveaux P
影响因子：
4.1
作者：
Dimmer, KS;Friedrich, B;Bröer, S
通讯作者：
Bröer, S
影响因子：
45.3
作者：
Bedikian, Agop Y.;Millward, Michael;Haluska, Frank G.
通讯作者：
Haluska, Frank G.
影响因子：
1.7
作者：
Nazarian, Rosalynn M.;Prieto, Victor G.;Duncan, Lyn M.
通讯作者：
Duncan, Lyn M.
DOI：
10.1073/pnas.1106123108
发表时间：
2011-10-04
影响因子：
11.1
作者：
Le Floch, Renaud;Chiche, Johanna;Pouyssegur, Jacques
通讯作者：
Pouyssegur, Jacques