Afatinib ameliorates osteoclast differentiation and function throughdownregulation of RANK signaling pathways

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/474351.do
DOI
10.5483/BMBRep.2017.50.3.223
Title
Afatinib ameliorates osteoclast differentiation and function throughdownregulation of RANK signaling pathways
Description
This work was supported by grants from the National Research Foundationof Korea (NRF) funded by the Ministry of Science, ICT, and FuturePlanning (MSIP-2008-0062282 and NRF2016R1A6A3A01006911).
abstract
Non-small-cell lung cancer (NSCLC) is the third most common cancer that spreads to the bone, resulting in osteolytic lesions caused by hyperactivation of osteoclasts. Activating mutations in epidermal growth factor receptor-tyrosine kinase (EGF-TK) are frequently associated with NSCLC, and afatinib is a first-line therapeutic drug, irreversibly targeting EGF-TK. However, the effects of afatinib on osteoclast differentiation and activation as well as the underlying mechanism remain unclear. In this study, afatinib significantly suppressed receptor activator of nuclear factor. B (RANK) ligand (RANKL)-induced osteoclast formation in bone marrow macrophages (BMMs). Consistently, afatinib inhibited the expression of osteoclast marker genes, whereas, it upregulated the expression of negative modulator genes. The bone resorbing activity of osteoclasts was also abrogated by afatinib. In addition, afatinib significantly inhibited RANKL-mediated Akt/protein kinase B and c-Jun N-terminal kinase phosphorylation. These results suggest that afatinib substantially suppresses osteoclastogenesis by downregulating RANK signaling pathways, and thus may reduce osteolysis after bone metastasis.
provenance
Made available in Cube on 2018-09-28T10:43:45Z (GMT). No. of bitstreams: 0
language
English
author
Ihn, Hye Jung
Kim, Ju Ang
Bae, Yong Chul
Shin, Hong-In
Baek, Moon-Chang
Park, Eui Kyun
accessioned
2018-09-28T10:43:45Z
available
2018-09-28T10:43:45Z
issued
2017
citation
BMB REPORTS(50): 3
issn
1976-6696
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/474351.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274068
Jurisdiction
Rep.of Korea
Project Name
KNU Bio-Medical Convergence Program for Creative Talent
rights
openAccess
subject
Afatinib
Bone resorption
Differentiation
Osteoclast
RANK signaling
type
article


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