Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz 90-647, Poland.
Oxid Med Cell Longev. 2019 Feb 3;2019:5729710. doi: 10.1155/2019/5729710. eCollection 2019.
Cancer is the second most frequent cause of death worldwide. It is considered to be one of the most dangerous diseases, and there is still no effective treatment for many types of cancer. Since cancerous cells have a high proliferation rate, it is pivotal for their proper functioning to have the well-functioning protein machinery. Correct protein processing and folding are crucial to maintain tumor homeostasis. Endoplasmic reticulum (ER) stress is one of the leading factors that cause disturbances in these processes. It is induced by impaired function of the ER and accumulation of unfolded proteins. Induction of ER stress affects many molecular pathways that cause the unfolded protein response (UPR). This is the way in which cells can adapt to the new conditions, but when ER stress cannot be resolved, the UPR induces cell death. The molecular mechanisms of this double-edged sword process are involved in the transition of the UPR either in a cell protection mechanism or in apoptosis. However, this process remains poorly understood but seems to be crucial in the treatment of many diseases that are related to ER stress. Hence, understanding the ER stress response, especially in the aspect of pathological consequences of UPR, has the potential to allow us to develop novel therapies and new diagnostic and prognostic markers for cancer.
癌症是全球第二大死亡原因。它被认为是最危险的疾病之一，对于许多类型的癌症仍然没有有效的治疗方法。由于癌细胞的增殖率很高，因此其正常功能的发挥对于功能正常的蛋白质机制至关重要。正确的蛋白质加工和折叠对于维持肿瘤内稳态至关重要。内质网（ER）应激是导致这些过程紊乱的主要因素之一。它是由 ER 功能障碍和未折叠蛋白质的积累引起的。ER 应激的诱导会影响许多导致未折叠蛋白反应（UPR）的分子途径。这是细胞适应新条件的方式，但当 ER 应激无法解决时，UPR 会诱导细胞死亡。这种双刃剑过程的分子机制涉及 UPR 的细胞保护机制或细胞凋亡的转变。然而，这一过程仍然知之甚少，但在与 ER 应激相关的许多疾病的治疗中似乎至关重要。因此，了解 ER 应激反应，特别是 UPR 的病理后果方面，有可能使我们能够开发针对癌症的新型治疗方法和新的诊断及预后标志物。
