Tashiro Etsu, Imoto Masaya
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama City 223-8522, Japan.
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama City 223-8522, Japan.
Bioorg Med Chem. 2016 Aug 1;24(15):3283-90. doi: 10.1016/j.bmc.2016.04.014. Epub 2016 Apr 7.
Cell migration is a fundamental step for embryonic development, wound repair, immune responses, and tumor cell invasion and metastasis. It is well known that protrusive structures, namely filopodia and lamellipodia, can be observed at the leading edge of migrating cells. The formation of these structures is necessary for cell migration; however, the molecular mechanisms behind the formation of these structures remain largely unclear. Therefore, bioactive compounds that modulate protrusive structures are extremely powerful tools for studying the mechanisms behind the formation of these structures and subsequent cell migration. Therefore, we have screened for bioactive compounds that inhibit the formation of filopodia, lamellipodia, or cell migration from natural products, and attempted to identify the target molecules of our isolated compounds. Additionally, autophagy is a bulk, non-specific protein degradation system that is involved in the pathogenesis of cancer and neurodegenerative disorders. Recent extensive studies have revealed the molecular mechanisms of autophagy, however, they also remain largely unclear. Thus, we also have screened for bioactive compounds that modulate autophagy, and identified the target molecules. In the present article, we introduce the phenotypic screening system and target identification of four bioactive compounds.
细胞迁移是胚胎发育、伤口修复、免疫反应以及肿瘤细胞侵袭和转移的一个基本步骤。众所周知,在迁移细胞的前沿可以观察到突出结构,即丝状伪足和片状伪足。这些结构的形成对于细胞迁移是必要的;然而,这些结构形成背后的分子机制在很大程度上仍不清楚。因此,调节突出结构的生物活性化合物是研究这些结构形成及后续细胞迁移背后机制的极其强大的工具。因此,我们从天然产物中筛选了抑制丝状伪足、片状伪足形成或细胞迁移的生物活性化合物,并试图鉴定我们分离出的化合物的靶分子。此外,自噬是一种大量的、非特异性的蛋白质降解系统,它参与癌症和神经退行性疾病的发病机制。最近的广泛研究揭示了自噬的分子机制,然而,这些机制在很大程度上也仍不清楚。因此,我们还筛选了调节自噬的生物活性化合物,并鉴定了靶分子。在本文中,我们介绍了四种生物活性化合物的表型筛选系统和靶标鉴定。