Laboratory of Molecular Basis of Cell Motility, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine.
Adv Exp Med Biol. 2020;1202:243-258. doi: 10.1007/978-3-030-30651-9_12.
The observations that numerous cancers are characterized by impairment in arginine synthesis and that deficit of exogenous arginine specifically affects their growth and viability are the ground for arginine deprivation-based anticancer treatment strategy. This review addresses molecular mechanisms of the human glioblastoma cell response to arginine deprivation. Our earlier studies have shown that arginine deprivation specifically impairs glioblastoma cell motility, adhesion and invasiveness. These changes were evoked by alterations in the actin cytoskeleton organization resulting from a decreased arginylation of β-actin isoform. Moreover, deficit of arginine induces prolonged endoplasmic reticulum (ER) stress and activation of the unfolded protein response, not leading, however, to a massive apoptosis in glioblastoma cells. Our current research indicates that cell death could be augmented by other compounds such as modulators of ER stress, for example arginine analogue of plant origin, canavanine. Implication of these studies on the development of new anti-glioma metabolic therapeutic modalities are discussed.
大量癌症的特征是精氨酸合成受损，而外源性精氨酸的缺乏特别影响其生长和活力，这是基于精氨酸剥夺的抗癌治疗策略的基础。本综述探讨了人胶质母细胞瘤细胞对精氨酸剥夺的反应的分子机制。我们之前的研究表明，精氨酸剥夺特异性地损害胶质母细胞瘤细胞的运动性、黏附和侵袭性。这些变化是由β-肌动蛋白同工型的精氨酸化减少导致的肌动蛋白细胞骨架组织的改变引起的。此外，精氨酸的缺乏会诱导内质网（ER）应激和未折叠蛋白反应的激活，但不会导致胶质母细胞瘤细胞大量凋亡。我们目前的研究表明，细胞死亡可以通过其他化合物如 ER 应激调节剂来增强，例如植物来源的精氨酸类似物，-canavanine。讨论了这些研究对开发新的抗胶质瘤代谢治疗模式的意义。
