Frolova Anastasia S, Petushkova Anastasiia I, Makarov Vladimir A, Soond Surinder M, Zamyatnin Andrey A
Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
Biology (Basel). 2020 Dec 19;9(12):480. doi: 10.3390/biology9120480.
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for the degradation of a wide range of extracellular matrix proteins, which are involved in many cellular processes to ensure the normal development of tissues and organs. Overexpression of MMPs has been observed to facilitate cellular growth, migration, and metastasis of tumor cells during cancer progression. A growing number of these proteins are being found to exist in the nuclei of both healthy and tumor cells, thus highlighting their localization as having a genuine purpose in cellular homeostasis. The mechanism underlying nuclear transport and the effects of MMP nuclear translocation have not yet been fully elucidated. To date, nuclear MMPs appear to have a unique impact on cellular apoptosis and gene regulation, which can have effects on immune response and tumor progression, and thus present themselves as potential therapeutic targets in certain types of cancer or disease. Herein, we highlight and evaluate what progress has been made in this area of research, which clearly has some value as a specific and unique way of targeting the activity of nuclear matrix metalloproteinases within various cell types.
基质金属蛋白酶（MMPs）是一类依赖锌的内肽酶，负责降解多种细胞外基质蛋白，这些蛋白参与许多细胞过程，以确保组织和器官的正常发育。在癌症进展过程中，已观察到MMPs的过表达促进肿瘤细胞的生长、迁移和转移。越来越多的这类蛋白被发现在健康细胞和肿瘤细胞的细胞核中都存在，从而突出了它们的定位在细胞稳态中具有真正的作用。核转运的潜在机制以及MMP核易位的影响尚未完全阐明。迄今为止，核MMPs似乎对细胞凋亡和基因调控有独特的影响，这可能会影响免疫反应和肿瘤进展，因此在某些类型的癌症或疾病中表现为潜在的治疗靶点。在此，我们重点介绍并评估了该研究领域取得的进展，这显然作为一种针对各种细胞类型内核基质金属蛋白酶活性的特定且独特的方式具有一定价值。
