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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2019 | NSCLC | Research

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

Authors: Wenjuan Wang, Yajie Xiong, Xinyuan Ding, Long Wang, Yifan Zhao, Yao Fei, Ying Zhu, Xiao Shen, Caihong Tan, Zhongqin Liang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2019

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.

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Title: Cathepsin L activated by mutant p53 and Egr-1 promotes ionizing radiation-induced EMT in human NSCLC
Authors: Wenjuan Wang
Yajie Xiong
Xinyuan Ding
Long Wang
Yifan Zhao
Yao Fei
Ying Zhu
Xiao Shen
Caihong Tan
Zhongqin Liang
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: NSCLC
Metastasis
Ionizing Radiation
NSCLC
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2019
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-019-1054-x

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