Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker

Cholangiocarcinoma (CCA) is a devastating disease due to resistance to traditional chemotherapies and radiotherapies. New therapeutic strategies against CCA are urgently needed. This study investigated the role of lipocalin-2 ( LCN2 ) in human cholangiocarcinoma as a potential therapeutic target and...

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Published inScientific reports Vol. 6; no. 1; p. 36138
Main Authors Chiang, Kun-Chun, Yeh, Ta-Sen, Wu, Ren-Chin, Pang, Jong-Hwei S., Cheng, Chi-Tung, Wang, Shang-Yu, Juang, Horng-Heng, Yeh, Chun-Nan
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 26.10.2016
Nature Publishing Group
Subjects
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Bile
Cancer
Cell cycle
Cholangiocarcinoma
Disease resistance
Humanities and Social Sciences
Lipocalin
Mesenchyme
Metastases
Metastasis
multidisciplinary
Myc protein
Radiation therapy
Science
Tumor suppressor genes
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Summary:Cholangiocarcinoma (CCA) is a devastating disease due to resistance to traditional chemotherapies and radiotherapies. New therapeutic strategies against CCA are urgently needed. This study investigated the role of lipocalin-2 ( LCN2 ) in human cholangiocarcinoma as a potential therapeutic target and diagnostic marker. So far, the role of LCN2 in cancer is still controversial and studies regarding the role of LCN2 in CCA are limited. LCN2 knockdown inhibited CCA cell growth in vitro and in vivo through induction of cell cycle arrest at G0/G1 phases and decreased metastatic potential due to repression of epithelial-mesenchymal transition (EMT). Overexpression of LCN2 in CCA cells increased cell metastatic potential. We showed for the first time that the N-myc downstream regulated gene 1 ( NDRG1 ) and NDRG2 , known as tumor suppressor genes, are negatively regulated by LCN2 in CCA cells. LCN2 concentration in bile was higher in patients with CCA than that in patients with gallstones, with a cutoff value of 20.08 ng/ml making this a potential diagnostic marker. Higher LCN2 expression was associated with worse survival in patients with CCA. LCN2 is a promising target for CCA treatment and bile LCN2 level is a potential diagnostic marker for CCA.
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These authors contributed equally to this work.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep36138