Overexpression of lipocalin 2 in human cervical cancer enhances tumor invasion

I. Hsiao Chung, Tzu I. Wu, Chia Jung Liao, Jin Yo Hu, Yang Hsiang Lin, Pei Ju Tai, Chyong Huey Lai, Kwang Huei Lin

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Cervical carcinoma is the third-most common cause of cancer-related deaths in women worldwide. However, the molecular mechanisms underlying the metastasis of cervical cancer are still unclear. Oligonucleotide microarrays coupled with bioinformatics analysis show that cytoskeletal remodeling and epithelial-to- mesenchymal transition (EMT) are significant pathways in clinical specimens of cervical cancer. In accord with clinical observations demonstrating ectopic expression of lipocalin 2 (LCN2), an oncogenic protein associated with EMT, in malignant tumors, was significantly upregulated in cervical cancer and correlated with lymph node metastasis. Overexpression of LCN2 enhanced tumor cell migration and invasion both in vitro and in vivo. Conversely, knockdown or neutralization of LCN2 reduced tumor cell migration and invasion. LCN2-induced migration was stimulated by activation of the EMT-associated proteins, Snail, Twist, N-cadherin, fibronectin, and MMP-9. Our findings collectively support a potential role of LCN2 in cancer cell invasion through the EMT pathway and suggest that LCN2 could be effectively utilized as a lymph node metastasis marker in cervical cancer.

Original languageEnglish
Pages (from-to)11113-11126
Number of pages14
JournalOncotarget
Volume7
Issue number10
DOIs
Publication statusPublished - 2016

Keywords

  • Cervical cancer
  • Invasion
  • Lipocalin2
  • Metastasis

ASJC Scopus subject areas

  • Oncology

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