Abstract
Kindlin-2 promotes carcinogenesis through regulation of cell-cell and cell-extracellular matrix adhesion. However, the role of Kindlin-2 in glioma has not been elucidated. We investigated Kindlin-2 expression in 188 human glioma tissue samples. High Kindlin-2 expression was correlated with high pathological grade and a worse prognosis. Kindlin-2 promoted glioma cell motility and proliferation both in vitro and in vivo. Importantly, Kindlin-2 activated the EGFR pathway and increased EGFR mRNA levels. In addition to up-regulating Y-box binding protein-1 (YB-1) and β-catenin expression, Kindlin-2 formed a transcriptional complex with YB-1 and β-catenin that bound to the EGFR promoter and enhanced transcription. The β-catenin/YB-1/EGFR pathway was required for Kindlin-2-mediated functions. Our data provide a better understanding of the mechanisms underlying glioma progression, and suggest that Kindlin-2 may be a biomarker and therapeutic target in glioma.
Highlights
Glioma is the most common and deadliest type of primary brain tumor [1]
We demonstrated that Kindlin-2 expressionwas positively correlated with clinical tumor grade in human glioma tissue samples
Kindlin-2 status was an independent risk factor, suggesting that Kindlin-2 expression can be an indicator of glioma patient prognosis
Summary
Glioma is the most common and deadliest type of primary brain tumor [1]. Recent advances in microsurgical therapy, radiotherapy, chemotherapy, and other glioma therapeutic strategies have improved the survival rate [2,3]. Kindlin-2 was shown to be involved in tumor progression. Guo et al demonstrated that Kindlin-2 was highly expressed in breast cancer and found that Kindlin-2 interacted with and stabilized EGFR to regulate breast cancer progression [16,17]. Kindlin-2 overexpression decreased proliferation and migration in colorectal carcinoma cells, while Kindlin-2 down-regulation promoted tumorigenicity in vitro and in vivo [21]. These may be attributed to the expression and function of Kindlin-2 varying among different types of cancers. We previously reported that Kindlin-2 attenuated cisplatin-induced apoptosis in human glioma cells in vitro through the AKT/JNK and AKT/p38 signaling pathways [22]. Whether Kindlin-2 has a critical role in glioma progression is unclear
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