GBP3 promotes glioma cell proliferation via SQSTM1/p62-ERK1/2 axis.
Guanylate binding proteins (GBPs) are interferon-inducible large GTPases and play a crucial role in cell-autonomous immunity. However, the biology function of GBPs in cancer remains elusive. GBP3 is specifically expressed in adult brain. Here we show that GBP3 is highly elevated in human glioma tumors and glioma cell lines. Overexpression of GBP3 dramatically increased glioma cell proliferation whereas silencing GBP3 by RNA interference produced opposite effects. We further showed that GBP3 expression was able to induce sequestosome-1(SQSTM1, also named p62) expression and activate extracellular signal-regulated kinase (ERK1/2). The SQSTM1-ERK1/2 signaling cascade was essential for GBP3-promoted cell growth because depletion of SQSTM1 markedly reduced the phosphorylated ERK1/2 levels and GBP3-mediated cell growth, and inhibition of mitogen-activated protein kinase/ERK kinase abolished GBP3-induced glioma cell proliferation. Consistently, GBP3 overexpression significantly promoted glioma tumor growth in vivo and its expression was inversely correlated with the survival rate of glioma patients. Taken together, these results for the first time suggest that GBP3 contributes to the proliferation of glioma cells via regulating SQSTM1-ERK1/2 pathway, and GBP3 might represent as a new potential therapeutic target against glioma.
['Xu|Hui|H|', 'Sun|Lili|L|', 'Zheng|Yanwen|Y|', 'Yu|Shuye|S|', 'Ou-Yang|Jia|J|', 'Han|Hui|H|', 'Dai|Xingliang|X|', 'Yu|Xiaoting|X|', 'Li|Ming|M|', 'Lan|Qing|Q|']
D000818:Animals D001921:Brain D001932:Brain Neoplasms D002453:Cell Cycle D045744:Cell Line, Tumor D049109:Cell Proliferation D005260:Female D019204:GTP-Binding Proteins D005910:Glioma D006801:Humans D020935:MAP Kinase Signaling System D008819:Mice, Nude D000071456:Sequestosome-1 Protein D015398:Signal Transduction D015854:Up-Regulation
GBP3 Glioma Cell proliferation ERK1/2 SQSTM1/p62