PBK attenuates paclitaxel‐induced autophagic cell death by suppressing p53 in H460 non‐small‐cell lung cancer cells

Abstract

PDZ‐binding kinase (PBK) has previously been shown to mediate chemoresistance of cancer cells to anticancer drugs. However, it remains unclear how PBK regulates paclitaxel‐induced cancer cell death. Here, we demonstrate that PBK hinders paclitaxel‐mediated autophagic cell death in H460 non‐small‐cell lung cancer cells. PBK knockdown increased apoptosis, autophagy, p53 level, and LC3 puncta upon paclitaxel treatment. Moreover, p53 expression facilitated an increase in the LC3‐II/LC3‐I ratio in response to paclitaxel, and PBK knockdown augmented paclitaxel‐mediated p53 transcriptional activity. Meanwhile, paclitaxel induced PBK‐mediated p53 nuclear export and its subsequent ubiquitination in control cells, but not in PBK knockdown cells. We conclude that PBK hampers paclitaxel‐induced autophagic cell death by suppressing p53, suggesting a potential role of PBK in p53‐mediated H460 cell death.

Keywords

• Mdm2
• non‐small‐cell lung cancer cells
• p53
• PBK
• ubiquitination