Research Papers:

Thyroid hormone-mediated regulation of lipocalin 2 through the Met/FAK pathway in liver cancer

I-Hsiao Chung _, Cheng-Yi Chen, Yang-Hsiang Lin, Hsiang-Cheng Chi, Pei-ju Tai, Chia-Jung Liao, Chung-Ying Tsai, Syuan-Ling Lin, Meng-Han Wu, Ching-Ying Chen and Kwang-Huei Lin

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2015; 6:15050-15064. https://doi.org/10.18632/oncotarget.3670

Metrics: PDF 2323 views  |   HTML 2474 views  |   ?  


I-Hsiao Chung1, Cheng-Yi Chen2, Yang-Hsiang Lin1, Hsiang-Cheng Chi1, Ya-Hui Huang3, Pei-Ju Tai1, Chia-Jung Liao1, Chung-Ying Tsai1, Syuan-Ling Lin1, Meng-Han Wu1, Ching-Ying Chen1, Kwang-Huei Lin1

1Department of Biochemistry, School of Medicine, Chang-Gung University, Taoyuan, Taiwan

2Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan

3Liver Research Center, Department of Hepato-Gastroenterology, Chang-Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

Correspondence to:

Kwang-Huei Lin, e-mail: [email protected]

Keywords: thyroid hormone receptor, LCN2, Met/FAK cascade

Received: December 02, 2014     Accepted: March 25, 2015     Published: April 10, 2015


The thyroid hormone, 3,3′,5-triiodo-L-thyronine (T3), regulates cell growth, development and differentiation via interactions with thyroid hormone receptors (TR), but the mechanisms underlying T3-mediated modulation of cancer progression are currently unclear. Lipocalin 2 (LCN2), a tumor-associated protein, is overexpressed in a variety of cancer types. Oligonucleotide microarray, coupled with proteomic analysis, has revealed that LCN2 is positively regulated by T3/TR. However, the physiological role and pathway of T3-mediated regulation of LCN2 in hepatocellular carcinogenesis remain to be characterized. Upregulation of LCN2 after T3 stimulation was observed in a time- and dose-dependent manner. Additionally, TRE on the LCN2 promoter was identified at positions -1444/-1427. Overexpression of LCN2 enhanced tumor cell migration and invasion, and conversely, its knockdown suppressed migration and invasion, both in vitro and in vivo. LCN2-induced migration occurred through activation of the Met/FAK cascade. LCN2 was overexpressed in clinical hepatocellular carcinoma (HCC) patients, compared with normal subjects, and positively correlated with TRα levels. Both TRα and LCN2 showed similar expression patterns in relation to survival rate, tumor grade, tumor stage and vascular invasion. Our findings collectively support a potential role of T3/TR in cancer progression through regulation of LCN2 via the Met/FAK cascade. LCN2 may thus be effectively utilized as a novel marker and therapeutic target in HCC.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 3670