Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan.
Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
Adv Exp Med Biol. 2020;1202:151-178. doi: 10.1007/978-3-030-30651-9_8.
Protein tyrosine kinases are enzymes that are capable of adding a phosphate group to specific tyrosines on target proteins. A receptor tyrosine kinase (RTK) is a tyrosine kinase located at the cellular membrane and is activated by binding of a ligand via its extracellular domain. Protein phosphorylation by kinases is an important mechanism for communicating signals within a cell and regulating cellular activity; furthermore, this mechanism functions as an "on" or "off" switch in many cellular functions. Ninety unique tyrosine kinase genes, including 58 RTKs, were identified in the human genome; the products of these genes regulate cellular proliferation, survival, differentiation, function, and motility. Tyrosine kinases play a critical role in the development and progression of many types of cancer, in addition to their roles as key regulators of normal cellular processes. Recent studies have revealed that RTKs such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), c-Met, Tie, Axl, discoidin domain receptor 1 (DDR1), and erythropoietin-producing human hepatocellular carcinoma (Eph) play a major role in glioma invasion. Herein, we summarize recent advances in understanding the role of RTKs in glioma pathobiology, especially the invasive phenotype, and present the perspective that RTKs are a potential target of glioma therapy.
蛋白质酪氨酸激酶是能够在靶蛋白的特定酪氨酸上添加磷酸基团的酶。受体酪氨酸激酶 (RTK) 是位于细胞膜上的一种酪氨酸激酶，通过其细胞外结构域与配体结合而被激活。激酶对蛋白质的磷酸化是细胞内信号传递和调节细胞活性的重要机制；此外，该机制在许多细胞功能中充当“开”或“关”的开关。人类基因组中鉴定出了 90 个独特的酪氨酸激酶基因，包括 58 个 RTK；这些基因的产物调节细胞增殖、存活、分化、功能和迁移。除了作为正常细胞过程的关键调节剂外，酪氨酸激酶在许多类型癌症的发生和发展中也起着至关重要的作用。最近的研究表明，表皮生长因子受体 (EGFR)、血小板衍生生长因子受体 (PDGFR)、c-Met、Tie、Axl、盘状结构域受体 1 (DDR1) 和促红细胞生成素产生的人肝癌 (Eph) 等 RTK 在神经胶质瘤的侵袭中起主要作用。在此，我们总结了近年来对 RTK 在神经胶质瘤病理生物学中的作用，特别是侵袭表型的理解进展，并提出了 RTK 是神经胶质瘤治疗的潜在靶点的观点。
