PDZ‐binding kinase inhibitor OTS514 suppresses the proliferation of oral squamous carcinoma cells

Abstract

ObjectivePDZ‐binding kinase (PBK) has been reported as a poor prognostic factor and is a promising molecular target for anticancer therapeutics. Here, we aimed to investigate the effect of specific PBK inhibitor OTS514 on the survival of OSCC cells.MethodsFour OSCC cell lines (HSC‐2, HSC‐3, SAS, and OSC‐19) were used to examine the effect of OTS514 on cell survival and apoptosis. DNA microarray analysis was conducted to investigate the effect of OTS514 on gene expression in OSCC cells. Gene set enrichment analysis was performed to identify molecular signatures related to the antiproliferative effect of OTS514.ResultsOTS514 decreased the cell survival of OSCC cells dose‐dependently, and administration of OTS514 readily suppressed the HSC‐2‐derived tumor growth in immunodeficient mice. Treatment with OTS514 significantly increased the number of apoptotic cells and caspase‐3/7 activity. Importantly, OTS514 suppressed the expression of E2F target genes with a marked decrease in protein levels of E2F1, a transcriptional factor. Moreover, TP53 knockdown attenuated OTS514‐induced apoptosis.ConclusionOTS514 suppressed the proliferation of OSCC cells by downregulating the expression of E2F target genes and induced apoptosis by mediating the p53 signaling pathway. These results highlight the clinical application of PBK inhibitors in the development of molecular‐targeted therapeutics against OSCC.

Phosphorylation of PBK at Thr9 by CDK5 correlates with invasion of prolactinomas

“…Through consulting the literature , we were particularly interested in PBK, which is overexpressed in several human malignancies 20–24 . By analyzing the amino acid sequence of PBK, we found that PBK at Thr9 may be the potential phosphorylation site of CDK5.…”

“…Through consulting the literature, we were particularly interested in PBK, which is overexpressed in several human malignancies. [20][21][22][23][24] By analyzing the amino acid sequence of PBK, we found that PBK at Thr9 may be the potential phosphorylation site of CDK5. To further verify that CDK5 phosphorylates PBK-T9, HEK293 cells were transfected with GFP-CDK5 and FLAG-PBK.…”