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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.    Electronic supplementary material  The online version of this article (10.1186/s13046-019-1054-x) contains supplementary material, which is available to authorized users.

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