Cited 7 times in

A multiplicity of anti-invasive effects of farnesyl transferase inhibitor SCH66336 in human head and neck cancer

Title
A multiplicity of anti-invasive effects of farnesyl transferase inhibitor SCH66336 in human head and neck cancer
Authors
Seung Hyun Oh;Ju-Hee Kang;Ho-Young Lee;Edward S. Kim;Ok-Hee Lee;Jong Kyu Woo
Issue Date
2012
Journal Title
International Journal of Cancer
ISSN
0020-7136
Citation
International Journal of Cancer, Vol.131(3) : 537~547, 2012
Abstract
Metastasis is a critical event in the progression of head and neck squamous cell carcinoma (HNSCC) and closely correlates with clinical outcome. We previously showed that the farnesyl transferase inhibitor SCH66336 has antitumor activities in HNSCC by inducing insulin-like growth factor binding protein 3 (IGFBP-3) secretion, which in turn inhibits tumor growth and angiogenesis. In this study, we found that SCH66336 at a sublethal dose for HNSCC inhibited the migration and invasion of HNSCC cells. The inhibitory effect of SCH66336 was associated with the blockade of the IGF-1 receptor (IGF-1R) pathway via suppressing IGF-1R itself and Akt expression. Consistent with previous work, induction of IGFBP-3 by SCH66336 also contributed in part to the anti-invasive effect. SCH66336 treatment also reduced the expression and activity of the urokinase-type plasminogen activator (uPA) and matrix metalloproteinase 2 (MMP-2), both important regulators of tumor metastasis. The effect of SCH66336 on uPA activity was inhibited partly by knockdown of IGFBP-3 using siRNA. The inhibitory effect of SCH66336 on migration or invasion was attenuated partly or completely by knockdown of IGFBP-3, Akt, or IGF-1R expression, respectively. Our results demonstrate that the IGF-1R pathway plays a major role in the proliferation, migration, and invasion of HNSCC cells, suggesting that therapeutic obstruction of the IGF-1R pathway would be a useful approach to treating patients with HNSCC.
URI

http://ir.ymlib.yonsei.ac.kr/handle/22282913/90444
DOI
10.1002/ijc.26373
Appears in Collections:
1. 연구논문 > 5. Research Institutes > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease
Yonsei Authors
사서에게 알리기
  feedback
Files in This Item:
T201205749.pdfDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse