Thyroid hormone-mediated regulation of lipocalin 2 through the Met/FAK pathway in liver cancer
| Autor: | I-Hsiao Chung, Cheng-Yi Chen, Yang-Hsiang Lin, Hsiang-Cheng Chi, Ya-Hui Huang, Pei-Ju Tai, Chia-Jung Liao, Chung-Ying Tsai, Syuan-Ling Lin, Meng-Han Wu, Ching-Ying Chen, Kwang-Huei Lin |
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| Rok vydání: | 2014 |
| Předmět: |
Thyroid Hormones
Blotting Western Transplantation Heterologous Mice SCID Biology medicine.disease_cause Response Elements LCN2 Downregulation and upregulation Lipocalin-2 Cell Movement Cell Line Tumor Proto-Oncogene Proteins Met/FAK cascade medicine Animals Humans Neoplasm Invasiveness Thyroid hormone receptor Triiodothyronine Receptors Thyroid Hormone Reverse Transcriptase Polymerase Chain Reaction Thyroid Liver Neoplasms Cancer thyroid hormone receptor Hep G2 Cells Proto-Oncogene Proteins c-met medicine.disease Lipocalins Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Focal Adhesion Kinase 1 Cancer research Liver cancer Carcinogenesis Hormone Acute-Phase Proteins Signal Transduction Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // I-Hsiao Chung 1 , Cheng-Yi Chen 2 , Yang-Hsiang Lin 1 , Hsiang-Cheng Chi 1 , Ya-Hui Huang 3 , Pei-Ju Tai 1 , Chia-Jung Liao 1 , Chung-Ying Tsai 1 , Syuan-Ling Lin 1 , Meng-Han Wu 1 , Ching-Ying Chen 1 , Kwang-Huei Lin 1 1 Department of Biochemistry, School of Medicine, Chang-Gung University, Taoyuan, Taiwan 2 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan 3 Liver Research Center, Department of Hepato-Gastroenterology, Chang-Gung Memorial Hospital, Linkou, Taoyuan, Taiwan Correspondence to: Kwang-Huei Lin, e-mail: khlin@mail.cgu.edu.tw Keywords: thyroid hormone receptor, LCN2, Met/FAK cascade Received: December 02, 2014 Accepted: March 25, 2015 Published: April 10, 2015 ABSTRACT The thyroid hormone, 3,3′,5-triiodo-L-thyronine (T 3 ), regulates cell growth, development and differentiation via interactions with thyroid hormone receptors (TR), but the mechanisms underlying T 3 -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 T 3 /TR. However, the physiological role and pathway of T 3 -mediated regulation of LCN2 in hepatocellular carcinogenesis remain to be characterized. Upregulation of LCN2 after T 3 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 T 3 /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. |
| Databáze: | OpenAIRE |
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