國家衛生研究院 NHRI:Item 3990099045/5373

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/5373

Title:	Focal adhesion Kinase as a therapeutic target of bortezomib
Authors:	Ko, BS;Chang, TC;Liou, JY
Contributors:	Institute of Cellular and Systems Medicine
Abstract:	Bortezomib, a modified dipeptidyl boronic acid, is a selective potent proteasome inhibitor that has been approved for clinical treatment of multiple myeloma and mantel cell lymphoma. Results from a growing number of basic studies and clinical trials reveal that bortezomib could be used to treat diverse types of solid tumors alone or in combination with other chemotherapeutic drugs. It has been shown that bortezomib transcriptionally suppresses focal adhesion kinase (FAK) expression by interrupting the nuclear factor kappa B (NFkappaB) pathway, which suggests that FAK could be a potential molecular target for bortezomib. Analysis of FAK promoter sequences revealed that FAK promoter harbors the NFkappaB and p53 binding domains. Further studies of FAK promoter activity, real-time PCR, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay revealed that bortezomib inhibits NFkappaB binding on the FAK promoter, thereby reducing FAK expression. Thus, bortezomib could inhibit cancer cell growth and migration or invasion by repressing FAK expression. Since activation and overexpression of FAK has been implicated in the progression and invasion of malignant tumors, it is likely that targeting FAK with bortezomib is a potential strategy for preventing cancer metastasis. This review focuses on the molecular regulation of FAK and the potential clinical application of bortezomib.
Date:	2010-12
Relation:	Anti-Cancer Agents in Medicinal Chemistry. 2010 Dec ;10(10):747-752.
Link to:	http://dx.doi.org/10.2174/187152010794728666
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1871-5206&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000288990800006
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79952752797
Appears in Collections:	[Jun-Yang Liou] Periodical Articles

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