期刊
CANCER LETTERS
卷 388, 期 -, 页码 167-176出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.11.037
关键词
Metastasis; Proliferation; Apoptosis; Methylation; Microarray
类别
资金
- National Natural Science Foundation of China [21575103, 81472683, 81201871]
- 863 Program [2015AA020403]
- National Key Scientific Instrument and Equipment Development Project [2013YQ16055106]
- Doctoral Research Fund from the Ministry of Education of China [20111202120016]
Hepatocellular carcinoma (HCC) invasion and metastasis are mediated by a complicated signal transduction network and downstream cytoskeletal and adhesion molecules. In this study, a microarray-based analysis revealed a dramatic increase in filamin C (FLNC), which is commonly expressed in muscle rather than in liver cells, in the two metastatic HCC cell lines MHCC97L and HCCLM3. Clinicopathological studies showed that increased FLNC expression was associated with microvascular invasion and poor prognosis. Specific hypomethylation was identified within the FLNC promoter region in HCC cell lines and patient tumor samples, which might contribute to the ectopic overexpression of FLNC. FLNC downregulation inhibited cell migration and impaired cell proliferation and promoted apoptosis. Mechanistic studies suggested that FLNC interacts with mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) and extracellular signal-regulated kinase 1/2 (ERK1/2) and that FLNC downregulation inhibited MEK1/2 and ERK1/2 activation. Xenographic tumor transplantation experiments in nude mice further confirmed the role of FLNC in HCC progression and metastasis. Our results reveal a novel mechanism by which the cytoskeletal protein FLNC enhances the mitogen-activated protein kinase signaling pathway during tumorigenesis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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