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Glioblastomas are the most common form of brain tumor. However, the molecular mechanisms that regulate tumor progression remain largely unknown. Kir7.1 (KCNJ7) is an inwardly rectifying potassium channel that is expressed at high levels in endothelial cells of brain tumors. Through heterologous expression, we found that Kir7.1 reduced glioblastoma cell proliferation and increased tumor cell apoptosis. We also evaluated the underlying molecular mechanisms in glioblastoma cells in vitro. Kir7.1 was found to inhibit Akt and Erk1/2 phosphorylation, cell growth, and cell cycle progression by directly phosphorylating S485 in the C terminus of Akt. Furthermore, our findings showed that endothelial cells can also act as major regulators of glioblastoma growth by secreting the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which binds to its receptor on glioblastoma cells to suppress glioblastoma cell growth and to induce cell apoptosis. The underlying mechanisms by which GM-CSF affects the growth of glioblastoma were investigated. GM-CSF was found to induce glioblastoma cell apoptosis by activating MAPK, and Kir7.1 was shown to enhance the growth-suppressive effects of GM-CSF by inhibiting the activation of the MAPK and Akt pathway. These data indicate that Kir7.1 can function as a tumor suppressor and that it promotes glioblastoma cell apoptosis and inhibits glioblastoma cell proliferation. Endothelial cells can also contribute to the development of glioblastomas. GM-CSF can induce the apoptosis of glioblastoma cells by activating the MAPK pathway, and Kir7.1 increases the efficacy of the growth-suppressive effects of GM-CSF by inhibiting Akt activation. Our findings shed light on the underlying

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