Increasing evidence has indicated that PDZ binding kinase (PBK) promotes proliferation, invasion, and therapeutic resistance in a variety of cancer types. However, the physiological function and therapy-resistant role of PBK in GBM remain underexplored. In this study, PBK was identified as one of the most therapy-resistant genes with significantly elevated expression level in GBM. Moreover, the high expression level of PBK was essential for GBM tumorigenesis and radio-resistance both in vitro and in vivo. Clinically, aberrant activation of PBK was correlated with poor clinical prognosis. In addition, inhibition of PBK dramatically enhanced the efficacy of radiation therapy in GBM cells. Mechanically, PBK-dependent transcriptional regulation of CCNB2 was critical for tumorigenesis and radio-resistance in GBM cells. Collectively, PBK promotes tumorigenesis and radio-resistance in GBM and may serve as a novel therapeutic target for GBM treatment.

越来越多的证据表明，PDZ结合激酶（PBK）可以促进多种癌症类型的增殖，侵袭和治疗抗性。然而，PBK在GBM中的生理功能和治疗抗性作用仍未得到充分研究。在这项研究中，PBK被确定为对治疗耐药性最高的基因之一，其在GBM中的表达水平显着升高。此外，PBK的高表达水平对于体外和体内GBM的肿瘤发生和放射抗性都是必不可少的。在临床上，PBK异常激活与不良的临床预后相关。此外，对PBK的抑制显着增强了GBM细胞中放射治疗的功效。从机械上讲，CCNB2的PBK依赖性转录调节对于GBM细胞的肿瘤发生和放射抗性至关重要。PBK共同促进GBM中的肿瘤发生和放射抗性，并且可以作为GBM治疗的新治疗靶标。