文章：

p66Shc蛋白——氧化应激传感器还是氧化还原酶：其在人类乳腺癌线粒体代谢中的潜在作用

p66Shc Protein—Oxidative Stress Sensor or Redox Enzyme: Its Potential Role in Mitochondrial Metabolism of Human Breast Cancer

原文发布日期：28 September 2024

DOI: 10.3390/cancers16193324

类型: Article

开放获取: 是

英文摘要：

This work presents a comprehensive evaluation of the role of p66Shc protein in mitochondrial physiology in MDA-MB-231 breast cancer cells. The use of human breast cancer cell line MDA-MB-231 and its genetically modified clones (obtained with the use of the CRISPR-Cas9 technique), expressing different levels of p66Shc protein, allowed us to demonstrate how the p66Shc protein affects mitochondrial metabolism of human breast cancer cells. Changes in the level of p66Shc (its overexpression, and overexpressing of its Serine 36-mutated version, as well as the knockout of p66Shc) exert different effects in breast cancer cells. Interestingly, knocking out p66Shc caused significant changes observed mostly in mitochondrial bioenergetic parameters. We have shown that an MDA-MB-231 (which is a strong metastatic type of breast cancer) clone lacking p66Shc protein is characterized by a significant shift in the metabolic phenotype in comparison to other MDA-MB-231 clones. Additionally, this clone is significantly more vulnerable to doxorubicin treatment. We have proved that p66Shc adaptor protein in human breast cancer cells may exert a different role than in noncancerous cells (e.g., fibroblasts).

摘要翻译： 

本研究系统评估了p66Shc蛋白在MDA-MB-231乳腺癌细胞线粒体生理功能中的作用。通过采用人乳腺癌细胞系MDA-MB-231及其基因修饰克隆（利用CRISPR-Cas9技术获得），这些细胞系表达不同水平的p66Shc蛋白，我们得以揭示p66Shc蛋白如何影响人乳腺癌细胞的线粒体代谢。p66Shc水平的变化（包括其过表达、丝氨酸36位点突变体过表达以及基因敲除）在乳腺癌细胞中产生不同的效应。值得注意的是，p66Shc敲除主要引起线粒体生物能量学参数的显著改变。研究显示，与其它MDA-MB-231克隆相比，缺失p66Shc蛋白的MDA-MB-231克隆（该细胞系属于高转移性乳腺癌类型）表现出显著的代谢表型转变。此外，该克隆对阿霉素治疗的敏感性显著增强。我们证实了p66Shc衔接蛋白在人乳腺癌细胞中可能发挥与非癌细胞（如成纤维细胞）不同的生物学功能。

原文链接：

p66Shc Protein—Oxidative Stress Sensor or Redox Enzyme: Its Potential Role in Mitochondrial Metabolism of Human Breast Cancer