Zinc finger protein 501 maintains glioblastoma cell growth through enhancing Frizzled-6 expression

Abstract

Understanding the regulatory mechanisms of glioblastoma growth is crucial for developing novel therapies. In this study, the expression and function of zinc finger protein 501 (ZNF501) in human glioblastoma cells were characterized. ZNF501 was abundantly expressed in human glioblastoma cell lines U251, U118, U87, and U138. ZNF501 ablation in these cell lines caused inhibition of proliferation, sphere formation, and the expression of SOX2 and OCT4. Besides, ZNF501 ablation increased the sensitivity of these cell lines to Temozolomide but did not influence cell migration. Orthotopic implantation of U251 cells and U118 cells indicated that ZNF501 ablation suppressed glioblastoma cell proliferation and tumor formation in vivo. ZNF501 ablation induced down-regulation of Frizzled-6 (FZD6), a component of the Wnt signaling. Lentivirus-mediated FZD6 overexpression restored the proliferation, sphere formation, drug sensitivity, and SOX2 and OCT4 expression in these cell lines. ZNF501 ablation also incurred down-regulation of JNK phosphorylation which is an indicator of the non-canonical Wnt signaling, but did not change the expression of active β-catenin which is the hallmark of the canonical Wnt signaling. Inhibition of the non-canonical Wnt signaling abrogated the effects of ZNF501 and FZD6. Therefore, for the first time, we showed that ZNF501 is essential for the growth and stemness of glioblastoma cells possibly by maintaining FZD6 expression and the non-canonical Wnt signaling.