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Differential inhibition of transmembrane 4 L six family member 5 (TM4SF5)-mediated tumorigenesis by TSAHC and sorafenib

Cited 12 time in Web of Science Cited 13 time in Scopus
Authors
Lee, Sin-Ae; Lee, Mi-Sook; Ryu, Hyung Won; Kwak, Tae Kyoung; Kang, Minkyung; Kim, Hyun Jeong; Lee, Jung Weon; Park, Ki Hun; Jung, Oisun; Kim, Hyeonjung
Issue Date
2011-02-01
Publisher
LANDES BIOSCIENCE
Citation
CANCER BIOLOGY & THERAPY, Vol.11, No.3, pp.330-336
Keywords
contact inhibitionTM4SF5sorafenibliver carcinomaanti-tumorigenic reagent
Abstract
Two separate clinical studies of advanced hepatocarcinoma patients recently reported that the multikinase inhibitor sorafenib (nexavar) could extend survival of the patients only by 2-3 months. We also previously demonstrated that 4`-(p-toluenesulfonylamido)-4-hydroxychalcone (TSAHC) blocks the multilayer growth and migration mediated by TM4SF5, which is highly expressed in approximately 80% of Korean hepatocarcinoma patients. Therefore, we wondered how TSAHC might be different from sorafenib to deal with hepatocarcinoma in terms of the therapeutic characteristics including specificity for TM4SF5. TM4SF5 is previously shown to mediate tumorigenesis through cytosolic p27(Kip1)-mediated inactivation of RhoA, epithelial-mesenchymal transition, multilayer growth, migration, invasion and tumor angiogenesis. In this study, TSAHC and two derivatives showed similar antagonistic activities against TM4SF5-mediated signaling and multilayer growth in vitro and anti-tumorigenic activity even in early stages of TM4SF5-mediated tumor formation in nude mice. Meanwhile, sorafenib was only effective much later in tumorigenesis in vivo and affected in vitro proliferation in a TM4SF5-independent manner. Altogether, these observations suggest that TSAHC may be a promising anti-tumorigenic reagent, especially against TM4SF5-mediated hepatocarcinoma.
ISSN
1538-4047
Language
English
URI
http://hdl.handle.net/10371/80534
DOI
https://doi.org/10.4161/cbt.11.3.14099
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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