Manganese Superoxide Dismutase Acetylation and Regulation of Protein Structure in Breast Cancer Biology and Therapy.

The loss and/or dysregulation of several cellular and mitochondrial antioxidants’ expression or enzymatic activity, which leads to the aberrant physiological function of these proteins, has been shown to result in oxidative damage to cellular macromolecules. In this regard, it has been surmised that the disruption of mitochondrial networks responsible for maintaining normal metabolism is an established hallmark of cancer and a novel mechanism of therapy resistance. This altered metabolism leads to aberrant accumulation of reactive oxygen species (ROS), which, under specific physiological conditions, leads to a potential tumor-permissive cellular environment. In this regard, it is becoming increasingly clear that the loss or disruption of mitochondrial oxidant scavenging enzymes may be, in specific tumors, either an early event in transformation or exhibit tumor-promoting properties. One example of such an antioxidant enzyme is manganese superoxide dismutase (MnSOD, also referred to as SOD2), which detoxifies superoxide, a ROS that has been shown, when its normal physiological levels are disrupted, to lead to oncogenicity and therapy resistance. Here, we will also discuss how the acetylation of MnSOD leads to a change in detoxification function that leads to a cellular environment permissive for the development of lineage plasticity-like properties that may be one mechanism leading to tumorigenic and therapy-resistant phenotypes.

几种细胞和线粒体抗氧化剂的表达或酶活性的缺失和/或失调会导致这些蛋白质生理功能异常，已表明这会造成细胞大分子的氧化损伤。在这方面，据推测，负责维持正常代谢的线粒体网络的破坏是癌症的一个既定特征，也是治疗耐药的一种新机制。这种代谢改变导致活性氧（ROS）的异常积累，在特定生理条件下，这会导致一种潜在的有利于肿瘤的细胞环境。在这方面，越来越清楚的是，线粒体抗氧化剂清除酶的缺失或破坏在特定肿瘤中可能是转化的早期事件，或者表现出促肿瘤特性。这种抗氧化酶的一个例子是锰超氧化物歧化酶（MnSOD，也称为SOD2），它能解毒超氧化物，超氧化物是一种ROS，当其正常生理水平被破坏时，已表明会导致致癌性和治疗耐药性。在此，我们还将讨论MnSOD的乙酰化如何导致解毒功能的改变，从而导致一种有利于细胞发生谱系可塑性样特性的细胞环境，这可能是导致致瘤和治疗耐药表型的一种机制。