Cathepsin L activated by mutant p53 and Egr-1 promotes ionizing radiation-induced EMT in human NSCLC

Journal of Experimental & Clinical Cancer Research

Yajie Xiong¹  Caihong Tan¹  Yifan Zhao¹  Ying Zhu¹  Long Wang¹  Yao Fei¹  Xiao Shen¹  Zhongqin Liang¹  Wenjuan Wang¹  Xinyuan Ding² 

[1] Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University;Institutes for Translational Medicine, Soochow University;

关键词: Non-small cell lung cancer;    Ionizing radiation;    Epithelial-mesenchymal transition;    p53 mutation;    Cathepsin L;   

DOI  :  10.1186/s13046-019-1054-x

来源: DOAJ

【 摘 要 】

Abstract Background Ionizing radiation (IR) is one of the major clinical therapies of cancer, although it increases the epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC), unexpectedly. The cellular and molecular mechanisms underlying this role are not completely understood. Methods We used NSCLC cell lines as well as tumor specimens from 78 patients with NSCLC to evaluate p53, Cathepsin L (CTSL) and EMT phenotypic changes. Xenograft models was also utilized to examine the roles of mutant p53 (mut-p53) and CTSL in regulating IR-induced EMT of NSCLC. Results Expression of CTSL was markedly increased in human NSCLC tissues with mutant p53 (mut-p53), and p53 mutation positively correlated with metastasis of NSCLC patients. In human non-small cell lung cancer cell line, H1299 cells transfected with various p53 lentivirus vectors, mut-p53 could promote the invasion and motility of cells under IR, mainly through the EMT. This EMT process was induced by elevating intranuclear CTSL which was regulated by mut-p53 depending on Early growth response protein-1 (Egr-1) activation. In the subcutaneous tumor xenograft model, IR promoted the EMT of the cancer cells in the presence of mut-p53, owing to increase expression and nuclear transition of its downstream protein CTSL. Conclusion Taken together, these data reveal the role of the mut-p53/Egr-1/CTSL axis in regulating the signaling pathway responsible for IR-induced EMT.

【 授权许可】

Unknown