EGFR amplification and mutations are the most common oncogenic events in GBM. EGFR overexpression correlates with GBM invasion, but the underlying mechanisms are poorly understood. In a previous study, we showed that AJAP1 is involved in regulating F-actin to inhibit the invasive ability of GBM. In addition, in a GBM cell line, the AJAP1 promoter was highly bound by H3K27me3 and, through bioinformatics analysis, we found that AJAP1 expression was negatively correlated with EGFR. In this study, we found that the pathway downstream of EGFR had a higher activation level in GBM cell lines, which led to excessive tumor suppressor silencing. Therefore, we deduced that in glioma cells, the pathway downstream of EGFR remodels the cytoskeleton via AJAP1 epigenetic silencing to enhance invasion. Furthermore, MK2206 reversed AJAP1 downregulation by inhibiting the EGFR pathway. In vivo, MK2206 also inhibited the proliferation and local invasion of 87-EGFRvIII. These data suggest that activation of the EGFR signal transduction pathway genetically silences anti-oncogenes to enhance GBM malignancy. MK2206 might be a promising therapeutic for EGFR/EGFRvIII-positive GBMs.
Relationship of F-actin distribution to development of polar shape in human polymorphonuclear neutrophils
The enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers is mediated by threshold levels of constitutive tyrosine phosphorylation and unattenuated signaling.
PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer
Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression.
The AMPK agonist AICAR inhibits the growth of EGFRvIII-expressing glioblastomas by inhibiting lipogenesis.
Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1.
MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo
Combination of farnesyltransferase and Akt inhibitors is synergistic in breast cancer cells and causes significant breast tumor regression in ErbB2 transgenic mice.
MK-2206, a novel allosteric inhibitor of Akt, synergizes with gefitinib against malignant glioma via modulating both autophagy and apoptosis.
Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors.
Erlotinib resistance in EGFR-amplified glioblastoma cells is associated with upregulation of EGFRvIII and PI3Kp110δ
Myosin IIA is critical for organelle distribution and F-actin organization in megakaryocytes and platelets.
AJAP1 is dysregulated at an early stage of gliomagenesis and suppresses invasion through cytoskeleton reorganization
Structure of the Complex of F-Actin and DNGR-1, a C-Type Lectin Receptor Involved in Dendritic Cell Cross-Presentation of Dead Cell-Associated Antigens
Competition for actin between two distinct F-actin networks defines a bistable switch for cell polarization
Modulation of EZH2 Expression by MEK-ERK or PI3K-AKT Signaling in Lung Cancer Is Dictated by Different KRAS Oncogene Mutations.
EGFRvIII/integrin β3 interaction in hypoxic and vitronectinenriching microenvironment promote GBM progression and metastasis
MiR-552 promotes the proliferation, migration and EMT of hepatocellular carcinoma cells by inhibiting AJAP1 expression
β-Catenin nuclear localization positively feeds back on EGF/EGFR-attenuated AJAP1 expression in breast cancer
Blocking LINC00152 suppresses glioblastoma malignancy by impairing mesenchymal phenotype through the miR-612/AKT2/NF-κB pathway
EGFR-vIII downregulated H2AZK4/7AC though the PI3K/AKT-HDAC2 axis to regulate cell cycle progression.
Dual Regulation of Histone Methylation by mTOR Complexes Controls Glioblastoma Tumor Cell Growth via EZH2 and SAM.
This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.