EphA3 is up-regulated by epidermal growth factor and promotes formation of glioblastoma cell aggregates.
EphA3 is up-regulated by epidermal growth factor and promotes formation of glioblastoma cell aggregates.
复制标题
DOI：
10.1016/j.bbrc.2018.12.002
复制
发表时间：
2019-01
影响因子：
3.1
通讯作者：
Moe Toyama;Yuho Hamaoka;H. Katoh
中科院分区：
文献类型：
--
作者：
Moe Toyama;Yuho Hamaoka;H. Katoh
EphA 3是受体酪氨酸激酶Eph家族的成员，据报道在包括胶质母细胞瘤在内的一些人类癌症中过表达。在这里，我们发现EphA 3的表达响应于表皮生长因子（EGF）刺激而上调，并促进胶质母细胞瘤细胞悬浮培养物中细胞聚集体的形成。通过短发夹RNA介导的敲低或CRISPR/Cas9介导的基因缺失抑制EphA 3表达抑制了EGF诱导的细胞聚集体形成的促进，而EphA 3的过表达促进了悬浮培养物中细胞聚集体的形成。EGF诱导的EphA 3表达和促进细胞聚集体形成需要Akt活性。此外，N-cadherin，其表达受EGF和EphA 3调节，有助于悬浮培养中细胞聚集体的形成。这些结果表明EphA 3表达的调节在非粘附条件下胶质母细胞瘤细胞生长中起关键作用。
EphA3, a member of the Eph family of receptor tyrosine kinases, has been reported to be overexpressed in some human cancers including glioblastoma. Here, we found that expression of EphA3 is up-regulated in response to epidermal growth factor (EGF) stimulation and promotes formation of cell aggregates in suspension culture of glioblastoma cells. Suppression of EphA3 expression by short hairpin RNA-mediated knockdown or CRISPR/Cas9-mediated gene deletion inhibited EGF-induced promotion of cell aggregate formation, whereas overexpression of EphA3 promoted formation of cell aggregates in suspension culture. EGF-induced EphA3 expression and promotion of cell aggregate formation required Akt activity. Furthermore, N-cadherin, whose expression was regulated by EGF and EphA3, contributed to the formation of cell aggregates in suspension culture. These results suggest that the regulation of EphA3 expression plays a critical role in glioblastoma cell growth in non-adherent conditions.