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Molecular Cancer
Published in: Molecular Cancer 1/2016

Open Access 01-12-2016 | Research

Lipocalin2 suppresses metastasis of colorectal cancer by attenuating NF-κB-dependent activation of snail and epithelial mesenchymal transition

Authors: Meibao Feng, Jieqiong Feng, Wuzhen Chen, Wubin Wang, Xuesong Wu, Jing Zhang, Fangying Xu, Maode Lai

Published in: Molecular Cancer | Issue 1/2016

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Abstract

Background

Lipocalin2 (LCN2) is a secretory protein that is aberrantly expressed in several types of cancer and has been involved in metastatic progression. However, neither mechanisms nor the role that LCN2 plays in the metastasis of colorectal cancer are clear.

Methods

LCN2 expression in colorectal cancer was detected by immunohistochemistry in 400 tissue specimens and Kaplan-Meier survival analysis was performed. In vitro, real-time PCR, western blot, colony formation assay, immunofluorescence assay, wound healing assay, migration and invasion experiment were performed to investigate the effects of LCN2 in epithelial mesenchymal transition (EMT), migration and invasion, respectively. In vivo mouse xenograft and metastasis models were utilized to determine tumorigenicity and metastasis ability, and immunohistochemistry, real-time PCR, western blot were used to evaluate the related protein expression. Luciferase reporter assay was used to explore the role of LCN2 on NF-ĸB promoter.

Results

LCN2 was highly expressed in 66.5% of the specimens, and significantly correlated with positive E-cadherin in the membrane and negative nuclear β-catenin. Higher expression of LCN2 together with negative NF-κB expression was negatively related to nuclear accumulation of snail and predicted favorable prognosis. LCN2 blocked cell proliferation, migration and invasion in vitro and in vivo, and inhibited translocation of NF-κB into nucleus. NF-κB could reverse the effect of LCN2 on EMT and promote snail expression. Rescued snail expression had similar effect without influencing NF-κB activity.

Conclusion

LCN2 may be an important negative regulator in EMT, invasion and metastasis of CRC via acting as upstream of NF-κB/snail signaling pathway. Thereby combinative manipulation of LCN2 and NF-κB/snail pathway may represent a novel and promising therapeutic approach for the patients with CRC.
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Metadata
Title
Lipocalin2 suppresses metastasis of colorectal cancer by attenuating NF-κB-dependent activation of snail and epithelial mesenchymal transition
Authors
Meibao Feng
Jieqiong Feng
Wuzhen Chen
Wubin Wang
Xuesong Wu
Jing Zhang
Fangying Xu
Maode Lai
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2016
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-016-0564-9

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