α-Catenin inhibits glioma cell migration, invasion, and proliferation by suppression of β-catenin transactivation.
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.
Ji
Haitao
H
Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Wang
Ji
J
Fang
Bingliang
B
Fang
Xuexun
X
Lu
Zhimin
Z
D002452:Cell Count / Q000379:methods; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014162:Transfection / Q000379:methods; D051178:alpha Catenin / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
D034741:RNA, Small Interfering; D051178:alpha Catenin; D051176:beta Catenin; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins