Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
J Neurooncol. 2011 Jul;103(3):445-51. doi: 10.1007/s11060-010-0413-4. Epub 2010 Sep 26.
Patients with glioblastomas, the most common primary tumors of the central nervous system, have poor prognoses because of uncontrolled tumor cell invasion and proliferation. β-Catenin plays an important role in tumor development. However, whether α-catenin expression contributes to β-catenin transactivation in glioma cells is largely unknown. We report here that α-catenin expression abrogates epidermal growth factor receptor (EGFR)-activation-induced β-catenin nuclear translocation in human glioblastoma cells, thereby attenuating β-catenin transactivation and the expression of its downstream genes CCND1 and c-myc. In addition, ectopic expression of α-catenin or depletion of β-catenin suppresses EGF-promoted glioblastoma cell migration, invasion, and proliferation. In contrast, α-catenin depletion promotes β-catenin nuclear translocation and transactivation, and tumor cell motility and growth. These findings reveal the importance of β-catenin regulation by α-catenin in cellular activities of glioblastoma cells.
患有神经胶质瘤（中枢神经系统最常见的原发性肿瘤）的患者预后不佳，这是因为肿瘤细胞不受控制的侵袭和增殖。β-连环蛋白在肿瘤的发生发展中起着重要作用。然而，α-连环蛋白的表达是否有助于神经胶质瘤细胞中β-连环蛋白的转录激活在很大程度上尚不清楚。我们在此报道，α-连环蛋白的表达可阻断表皮生长因子受体（EGFR）激活诱导的人神经胶质瘤细胞中β-连环蛋白的核易位，从而减弱β-连环蛋白的转录激活及其下游基因 CCND1 和 c-myc 的表达。此外，α-连环蛋白的异位表达或β-连环蛋白的耗竭均可抑制 EGF 促进的神经胶质瘤细胞的迁移、侵袭和增殖。相反，α-连环蛋白的耗竭可促进β-连环蛋白的核易位和转录激活，并增强肿瘤细胞的运动性和生长。这些发现揭示了α-连环蛋白对神经胶质瘤细胞细胞活动中β-连环蛋白的调节的重要性。
