國家衛生研究院 NHRI:Item 3990099045/1643

NHRI > Institute of Cellular and Systems Medicine > Shan-Kung Lin(2004-2017) > Periodical Articles > Item 3990099045/1643

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/1643

Title:	Hypoxia-inducible factor 1 alpha regulates lung adenocarcinoma cell invasion
Other Titles:	Hypoxia-inducible factor 1α regulates lung adenocarcinomacell invasion
Authors:	Shyu, KG;Hsu, FL;Wang, MJ;Wang, BW;Lin, S
Contributors:	Division of Gerontology Research
Abstract:	We studied the role of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in human lung adenocarcinoma cell invasion using a metastatic cell model composed of low invasive CL1 and highly invasive CLI-5 cells. We showed that HIF-1 alpha was expressed in CL1-5 but not in CL1 cells under normoxic condition, and that inhibition of HIF-1 alpha expression by a small interfering RNA decreased invasiveness of CL1-5 cells. Complementary, overexpression of HIF-1 alpha increased the invasiveness of CL1 and gastric cancer SC-M1 cells. Subsequently, we showed that urokinase-type plasminogen activator receptor (uPAR), and matrix metalloproteinases (MMPs) 1 and 2 were critical in HIF-1 alpha-induced invasion. Mechanistic studies revealed that HIF-1 alpha overexpression could increase the expression of UPAR and MMP1, but not MMP2. However, ELISA assays on the conditioned media generated from control CL1 and CL1 cells overexpressing HIF-1 alpha showed that overexpression of HIF-1 alpha increased the levels of endogenous free active MMP2 and total free MMP2, and the former was blocked by inhibition of MMPI expression. We conclude that (i) HIF-1 alpha overexpression enhances lung cancer cell invasion at least through up-regulating the expression and activities of uPAR, MMP1, and MMP2; and (ii) induction of MMP1 participates in cell invasion and also plays an important role in HIF-1 alpha-induced activation of MMP2. (c) 2007 Elsevier Inc. All rights reserved.
Keywords:	Oncology;Cell Biology
Date:	2007-04-01
Relation:	Experimental Cell Research. 2007 Apr;313(6):1181-1191.
Link to:	http://dx.doi.org/10.1016/j.yexcr.2007.01.013
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0014-4827&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000245412300010
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33947307906
Appears in Collections:	[Shan-Kung Lin(2004-2017)] Periodical Articles

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