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http://dx.doi.org/10.14348/molcells.2017.0104

The Candidate Tumor Suppressor Gene SLC8A2 Inhibits Invasion, Angiogenesis and Growth of Glioblastoma  

Qu, Mingqi (Department of Neurosurgery, Henan Provincial People's Hospital)
Yu, Ju (Department of Neurosurgery, the Second Affiliated Hospital of Soochow University)
Liu, Hongyuan (Department of Neurosurgery, Mianyang Central Hospital)
Ren, Ying (Department of Pathology, People's Hospital of Zhengzhou University)
Ma, Chunxiao (Department of Neurosurgery, Henan Provincial People's Hospital)
Bu, Xingyao (Department of Neurosurgery, Henan Provincial People's Hospital)
Lan, Qing (Department of Neurosurgery, the Second Affiliated Hospital of Soochow University)
Publication Information
Molecules and Cells / v.40, no.10, 2017 , pp. 761-772 More about this Journal
Abstract
Glioblastoma is the most frequent and most aggressive brain tumor in adults. Solute carrier family 8 member 2 (SLC8A2) is only expressed in normal brain, but not present in other human normal tissues or in gliomas. Therefore, we hypothesized that SLC8A2 might be a glioma tumor suppressor gene and detected the role of SLC8A2 in glioblastoma and explored the underlying molecular mechanism. The glioblastoma U87MG cells stably transfected with the lentivirus plasmid containg SLC8A2 (U87MG-SLC8A2) and negative control (U87MG-NC) were constructed. In the present study, we found that the tumorigenicity of U87MG in nude mice was totally inhibited by SLC8A2. Overexpression of SLC8A2 had no effect on cell proliferation or cell cycle, but impaired the invasion and migration of U87MG cells, most likely through inactivating the extracellular signal-related kinases (ERK)1/2 signaling pathway, inhibiting the nuclear translocation and DNA binding activity of nuclear factor kappa B ($NF-{\kappa}B$), reducing the level of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA)-its receptor (uPAR) system (ERK1/2-$NF-{\kappa}B$-MMPs/uPA-uPAR), and altering the protein levels of epithelial to mesenchymal transitions (EMT)-associated proteins E-cardherin, vimentin and Snail. In addition, SLC8A2 inhibited the angiogenesis of U87MG cells, probably through combined inhibition of endothelium-dependent and endothelium-nondependent angiogenesis (vascular mimicry pattern). Totally, SLC8A2 serves as a tumor suppressor gene and inhibits invasion, angiogenesis and growth of glioblastoma.
Keywords
angiogenesis; glioblastoma; growth; invasion; SLC8A2; U87MG;
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