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转移性三阴性乳腺癌与融合的线粒体形态以及糖酵解和脂生成代谢密切相关。

Metastatic TNBC is closely associated with a fused mitochondrial morphology and a glycolytic and lipogenic metabolism.

机构信息

Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, GIEE Medicina Cardiovascular y Metabólica, Nuevo Leon, Mexico.

Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, GIEE Investigación en Cáncer, Nuevo Leon, Mexico.

出版信息

Biochem Cell Biol. 2021 Aug;99(4):447-456. doi: 10.1139/bcb-2020-0439. Epub 2020 Dec 20.

Abstract

Mitochondria modify their function and morphology to satisfy the bioenergetic demand of the cells. Cancer cells take advantage of these features to sustain their metabolic, proliferative, metastatic, and survival necessities. Understanding the morphological changes to mitochondria in the different grades of triple-negative breast cancer (TNBC) could help to design new treatments. Consequently, this research explored mitochondrial morphology and the gene expression of some proteins related to mitochondrial dynamics, as well as proteins associated with oxidative and non-oxidative metabolism in metastatic and non-metastatic TNBC. We found that mitochondrial morphology and metabolism are different in metastatic and non-metastatic TNBC. In metastatic TNBC, there is overexpression of genes related to mitochondrial dynamics, fatty-acid metabolism, and glycolysis. These features are accompanied by a fused mitochondrial morphology. By comparison, in non-metastatic TNBC, there is a stress-associated mitochondrial morphology with hyperfragmented mitochondria, accompanied by the upregulated expression of genes associated with the biogenesis of mitochondria; both of which are characteristics related to the higher production of reactive oxygen species observed in this cell line. These differences between metastatic and non-metastatic TNBC should provide a better understanding of metastasis and contribute to the development of improved specific and personalized therapies for TNBC.

摘要

线粒体可以改变其功能和形态以满足细胞的能量需求。癌细胞利用这些特性来维持其代谢、增殖、转移和生存的需要。了解三阴性乳腺癌 (TNBC) 不同分级中线粒体的形态变化,有助于设计新的治疗方法。因此,本研究探讨了转移性和非转移性 TNBC 中线粒体形态和一些与线粒体动力学相关的蛋白以及与氧化和非氧化代谢相关的蛋白的基因表达。我们发现转移性和非转移性 TNBC 中的线粒体形态和代谢存在差异。在转移性 TNBC 中,与线粒体动力学、脂肪酸代谢和糖酵解相关的基因表达过度。这些特征伴随着融合的线粒体形态。相比之下,在非转移性 TNBC 中,存在应激相关的线粒体形态,线粒体超片段化,同时伴随着与线粒体生物发生相关的基因表达上调;这两种特征都与该细胞系中观察到的更高活性氧产生有关。转移性和非转移性 TNBC 之间的这些差异应该为转移提供更好的理解,并有助于开发针对 TNBC 的更特异和个性化的治疗方法。

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