Mitochondrial oxidative phosphorylation in cutaneous melanoma.
Mitochondrial oxidative phosphorylation in cutaneous melanoma.
复制标题
皮肤黑色素瘤的线粒体氧化磷酸化。
DOI：
10.1038/s41416-020-01159-y
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发表时间：
2021-01
影响因子：
8.8
通讯作者：
Moncrieff MD
中科院分区：
文献类型：
--
作者：
Kumar PR;Moore JA;Bowles KM;Rushworth SA;Moncrieff MD
肿瘤细胞中的瓦尔堡效应与糖酵解的上调以产生ATP有关，即使在含氧量正常的条件下和存在功能齐全的线粒体的情况下也是如此。然而，过去15年的科学进步改变了这一观点，证明了氧化磷酸化（OXPHOS）以及糖酵解在恶性细胞中的重要性。黑色素瘤中的代谢表型显示糖酵解和OXPHOS之间的异源动力学（代谢可塑性），赋予生存优势以适应恶劣条件和化学抗性途径。此外，OXPHOS和糖酵解（代谢共生）的同时上调已被证明对黑色素瘤进展至关重要。肿瘤微环境（TME）在促进黑色素瘤的进展、侵袭和转移中具有重要的支持作用。TME中的间充质基质细胞（MSC）显示出与黑色素瘤的共生关系，保护肿瘤细胞免于凋亡并赋予化学抗性。随着OXPHOS在代谢可塑性和共生中的重要作用，我们的综述概述了从间充质干细胞到黑色素瘤肿瘤细胞的线粒体转移如何在黑色素瘤进展中发挥关键作用，并且是黑色素瘤细胞即使在线粒体突变的存在下也能恢复OXPHOS能力的机制。在这篇综述中概述的研究表明，针对线粒体运输是一种潜在的新的治疗方法，这种高度难治性疾病。
The Warburg effect in tumour cells is associated with the upregulation of glycolysis to generate ATP, even under normoxic conditions and the presence of fully functioning mitochondria. However, scientific advances made over the past 15 years have reformed this perspective, demonstrating the importance of oxidative phosphorylation (OXPHOS) as well as glycolysis in malignant cells. The metabolic phenotypes in melanoma display heterogeneic dynamism (metabolic plasticity) between glycolysis and OXPHOS, conferring a survival advantage to adapt to harsh conditions and pathways of chemoresistance. Furthermore, the simultaneous upregulation of both OXPHOS and glycolysis (metabolic symbiosis) has been shown to be vital for melanoma progression. The tumour microenvironment (TME) has an essential supporting role in promoting progression, invasion and metastasis of melanoma. Mesenchymal stromal cells (MSCs) in the TME show a symbiotic relationship with melanoma, protecting tumour cells from apoptosis and conferring chemoresistance. With the significant role of OXPHOS in metabolic plasticity and symbiosis, our review outlines how mitochondrial transfer from MSCs to melanoma tumour cells plays a key role in melanoma progression and is the mechanism by which melanoma cells regain OXPHOS capacity even in the presence of mitochondrial mutations. The studies outlined in this review indicate that targeting mitochondrial trafficking is a potential novel therapeutic approach for this highly refractory disease.
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影响因子：
20.3
作者：
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通讯作者：
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影响因子：
4.1
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影响因子：
2.6
作者：
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通讯作者：
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