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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2021 | Pityriasis Lichenoides Chronica | Research

Elafin promotes tumour metastasis and attenuates the anti-metastatic effects of erlotinib via binding to EGFR in hepatocellular carcinoma

Authors: Chenwei Wang, Yadi Liao, Wei He, Hong Zhang, Dinglan Zuo, Wenwu Liu, Zhiwen Yang, Jiliang Qiu, Yichuan Yuan, Kai Li, Yuanping Zhang, Yongjin Wang, Yunxing Shi, Yuxiong Qiu, Song Gao, Yunfei Yuan, Binkui Li

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Background

Elafin is a serine protease inhibitor critical for host defence. We previously reported that Elafin was associated with the recurrence of early-stage hepatocellular carcinoma (HCC) after surgery. However, the exact role of Elafin in HCC remains obscure.

Methods

HCC tissue microarrays were used to investigate the correlation between Elafin expression and the prognosis of HCC patients. In vitro migration, invasion and wound healing assays and in vivo lung metastasis models were used to determine the role of Elafin in HCC metastasis. Mass spectrometry, co-immunoprecipitation, western blotting, and immunofluorescence staining assays were performed to uncover the mechanism of Elafin in HCC. Dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the transcriptional regulation of Elafin.

Results

Elafin expression was frequently increased in HCC tissues compared to normal tissues, and high Elafin expression in HCC tissues was correlated with aggressive tumour phenotypes and a poor prognosis in HCC patients. Elafin dramatically enhanced the metastasis of HCC cells both in vitro and in vivo by interacting with EGFR and activating EGFR/AKT signalling. Moreover, Elafin attenuated the suppressive effects of erlotinib on HCC metastasis. Besides, Elafin was transcriptionally regulated by Sp1 in HCC cells. Clinically, Elafin expression was positively correlated with Sp1, Vimentin, and EGFR signalling in both our HCC tissue microarrays and TCGA database analysis.

Conclusions

Upregulation of Elafin by Sp1 enhanced HCC metastasis via EGFR/AKT pathway, and overexpression of Elafin attenuated the anti-metastatic effects of erlotinib, suggesting a valuable prognostic biomarker and therapeutic target for HCC.

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Title: Elafin promotes tumour metastasis and attenuates the anti-metastatic effects of erlotinib via binding to EGFR in hepatocellular carcinoma
Authors: Chenwei Wang
Yadi Liao
Wei He
Hong Zhang
Dinglan Zuo
Wenwu Liu
Zhiwen Yang
Jiliang Qiu
Yichuan Yuan
Kai Li
Yuanping Zhang
Yongjin Wang
Yunxing Shi
Yuxiong Qiu
Song Gao
Yunfei Yuan
Binkui Li
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Pityriasis Lichenoides Chronica
Metastasis
Hepatocellular Carcinoma
Hepatocellular Carcinoma
Erlotinib
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-01904-y

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