Department of General Biology, Michaelideion Cardiac Centre, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.
Department of General Biology, Michaelideion Cardiac Centre, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.
Int J Oncol. 2019 Mar;54(3):821-832. doi: 10.3892/ijo.2018.4666. Epub 2018 Dec 12.
Heat shock protein 70 (Hsp70; also known as HSP70A1A) is one of the most induced proteins in cancer cells; however, its role in cancer has not yet been fully elucidated. In the present study, we proposed a hypothetical model in which the silencing of Hsp70 enhanced the metastatic properties of the HeLa, A549 and MCF7 cancer cell lines. We consider that the inability of cells to form cadherin‑catenin complexes in the absence of Hsp70 stimulates their detachment from neighboring cells, which is the first step of anoikis and metastasis. Under these conditions, an epithelial‑to‑mesenchymal transition (EMT) pathway is activated that causes cancer cells to acquire a mesenchymal phenotype, which is known to possess a higher ability for migration. Therefore, we herein provide evidence of the dual role of Hsp70 which, according to international literature, first establishes a cancerous environment and then, as suggested by our team, regulates the steps of the metastatic process, including EMT and migration. Finally, the trigger for the anti‑metastatic properties that are acquired by cancer cells in the absence of Hsp70 appears to be the destruction of the Hsp70‑dependent heterocomplexes of E‑cadherin/catenins, which function like an anchor between neighboring cells.
热休克蛋白 70（Hsp70；也称为 HSP70A1A）是癌细胞中诱导表达最多的蛋白之一；然而，其在癌症中的作用尚未完全阐明。在本研究中，我们提出了一个假设模型，即 Hsp70 的沉默增强了 HeLa、A549 和 MCF7 癌细胞系的转移特性。我们认为，在没有 Hsp70 的情况下，细胞无法形成钙粘蛋白-连环蛋白复合物，这会刺激它们从相邻细胞中脱离，这是细胞凋亡和转移的第一步。在这些条件下，上皮-间充质转化（EMT）途径被激活，导致癌细胞获得间充质表型，众所周知，间充质表型具有更高的迁移能力。因此，我们在此提供了 Hsp70 双重作用的证据，根据国际文献，Hsp70 首先建立了癌症环境，然后，正如我们团队所建议的，调节转移过程的步骤，包括 EMT 和迁移。最后，似乎是破坏了 Hsp70 依赖性 E-钙粘蛋白/连环蛋白异源复合物，这些复合物在相邻细胞之间充当类似锚的作用，导致缺乏 Hsp70 的癌细胞获得了抗转移特性。
