Laboratory of Molecular Neurobiology, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Laboratory of Molecular Neurobiology, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Cell Signal. 2019 Oct;62:109329. doi: 10.1016/j.cellsig.2019.05.014. Epub 2019 May 29.
EphA2, which belongs to the Eph family of receptor tyrosine kinases, is overexpressed in a variety of human cancers. Serine 897 (S897) phosphorylation of EphA2 is known to promote cancer cell migration and proliferation in a ligand-independent manner. In this study, we show that glucose deprivation induces S897 phosphorylation of EphA2 in glioblastoma cells. The phosphorylation requires the activity of the cystine/glutamate antiporter xCT and reactive oxygen species (ROS)-dependent ERK and RSK activation. Furthermore, depletion of EphA2 in glioblastoma cells leads to decreased cell viability under glucose starvation. Our results suggest a role of EphA2 in glioblastoma cell viability under glucose-limited conditions.
EphA2 属于受体酪氨酸激酶 Eph 家族，在多种人类癌症中过表达。EphA2 的丝氨酸 897（S897）磷酸化已知可在无配体的情况下促进癌细胞迁移和增殖。在这项研究中，我们表明葡萄糖剥夺可诱导神经胶质瘤细胞中 EphA2 的 S897 磷酸化。这种磷酸化需要半胱氨酸/谷氨酸反向转运蛋白 xCT 的活性以及依赖活性氧 (ROS) 的 ERK 和 RSK 的激活。此外，在神经胶质瘤细胞中耗尽 EphA2 会导致在葡萄糖饥饿下细胞活力下降。我们的结果表明 EphA2 在葡萄糖限制条件下的神经胶质瘤细胞活力中起作用。
