Lipocalin 2 promotes the migration and invasion of esophageal squamous cell carcinoma cells through a novel positive feedback loop

Ze-Peng Du; Bing-Li Wu; Yang-Min Xie; Ying-Li Zhang; Lian-Di Liao; Fei Zhou; Jian-Jun Xie; Fa-Min Zeng; Xiu-E Xu; Wang-Kai Fang; En-Min Li; Li-Yan Xu

doi:10.1016/j.bbamcr.2015.07.007

Lipocalin 2 promotes the migration and invasion of esophageal squamous cell carcinoma cells through a novel positive feedback loop

Biochim Biophys Acta. 2015 Oct;1853(10 Pt A):2240-50. doi: 10.1016/j.bbamcr.2015.07.007. Epub 2015 Jul 17.

Authors

Ze-Peng Du¹, Bing-Li Wu², Yang-Min Xie³, Ying-Li Zhang², Lian-Di Liao⁴, Fei Zhou³, Jian-Jun Xie², Fa-Min Zeng², Xiu-E Xu⁴, Wang-Kai Fang², En-Min Li⁵, Li-Yan Xu⁶

Affiliations

¹ The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China; Department of Pathology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou 515041, Guangdong Province 515041, China.
² The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China.
³ The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Department of Experimental Animal Center, Shantou University Medical College, Shantou 515041, China.
⁴ The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China.
⁵ The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China. Electronic address: nmli@stu.edu.cn.
⁶ The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China. Electronic address: lyxu@stu.edu.cn.

PMID: 26190820
DOI: 10.1016/j.bbamcr.2015.07.007

Abstract

Lipocalin 2 (LCN2) is a poor prognostic factor in esophageal squamous cell carcinoma (ESCC), however its functional roles and molecular mechanisms of action remain to be clarified. Here, we described the functions and signaling pathways for LCN2 in ESCC. Overexpression of LCN2 in ESCC cells accelerated cell migration and invasion in vitro, and promoted lung metastasis in vivo. Blocking LCN2 expression inhibited its pro-oncogenic effect. Either overexpression of LCN2 or treatment with recombinant human LCN2 protein enhanced the activation of MEK/ERK pathway, which in turn increases endogenous LCN2 to increase MMP-9 activity. The decreased p-cofilin and increased p-ERM induced by pERK1/2 cause the cytoskeleton F-actin rearrangement and alter the behavior of ESCC cells mediated by LCN2. As a consequence, activation of MMP-9 and the rearrangement of F-actin throw light on the mechanisms for LCN2 in ESCC. These results imply that LCN2 promotes the migration and invasion of ESCC cells through a novel positive feedback loop.

Keywords: Esophageal squamous cell carcinoma; Lipocalin 2; Migration and invasion of cancer cells; Positive feedback.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / genetics
Actins / metabolism
Acute-Phase Proteins / genetics
Acute-Phase Proteins / metabolism*
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / pathology
Cell Line, Tumor
Cell Movement*
Cytoskeleton / genetics
Cytoskeleton / metabolism
Esophageal Neoplasms / genetics
Esophageal Neoplasms / metabolism*
Esophageal Neoplasms / pathology
Humans
Lipocalin-2
Lipocalins / genetics
Lipocalins / metabolism*
MAP Kinase Signaling System*
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinase 9 / metabolism
Mitogen-Activated Protein Kinase 1 / genetics
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / genetics
Mitogen-Activated Protein Kinase 3 / metabolism
Neoplasm Invasiveness / genetics
Neoplasm Invasiveness / pathology
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*

Substances

Actins
Acute-Phase Proteins
LCN2 protein, human
Lipocalin-2
Lipocalins
Neoplasm Proteins
Proto-Oncogene Proteins
MAPK1 protein, human
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
MMP9 protein, human
Matrix Metalloproteinase 9