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2017 ; 40
(10
): 761-772
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gab.com Text
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The Candidate Tumor Suppressor Gene SLC8A2 Inhibits Invasion, Angiogenesis and
Growth of Glioblastoma
#MMPMID29047259
Qu M
; Yu J
; Liu H
; Ren Y
; Ma C
; Bu X
; Lan Q
Mol Cells
2017[Oct]; 40
(10
): 761-772
PMID29047259
show ga
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-?B), reducing the level of matrix
metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA)-its
receptor (uPAR) system (ERK1/2-NF-?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.