PPDPF Promotes the Progression and acts as an Antiapoptotic Protein in Non-Small Cell Lung Cancer
Yun Mu, Yingzi Li, Gao Jie, Liu Guanxin, Zimei Zeng, Zhen Cao, Zhi Li, Nie Yingjie, Lunquan Sun, Tao Chen, Deng Yuezhen, Zhou Cheng-zhi
Abstract
Resistance to radiotherapy is frequently observed in the clinic and leads to poor prognosis of non-small cell lung cancer (NSCLC). How to overcome resistance to radiotherapy is a challenge in the treatment of NSCLC. In this study, PPDPF was found to be upregulated in NSCLC tissues and cell lines, and its expression negatively correlated with the overall survival of patients with NSCLC. PPDPF promoted the growth, colony formation and invasion of lung cancer cells. Moreover, knockout of PPDPF inhibited tumorigenesis in the KL (Kras G12D ; LKB1 f/f ) mouse model of lung cancer. Additionally, overexpression of PPDPF led to radioresistance in lung cancer cells, and knockdown of PPDPF sensitized lung cancer cells to radiotherapy. Mechanistically, PPDPF interacted with BABAM2 (an antiapoptotic protein) and blocked its ubiquitination by MDM2, thus stabilizing BABAM2 and promoting the radioresistance of lung cancer cells. Our present study suggested PPDPF as a therapeutic target in NSCLC.