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

作者：Lee Sin Ae; Lee Mi Sook; Ryu Hyung Won; Kwak Tae Kyoung; Kim Hyeonjung; Kang Minkyung; Jung Oisun; Kim Hyun Jeong; Park Ki Hun; Lee Jung Weon^*

来源：Cancer Biology and Therapy, 2011, 11(3): 330-336.

DOI：10.4161/cbt.11.3.14099

• contact inhibition
• anti-tumorigenic reagent
• liver carcinoma
• sorafenib
• TM4SF5

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.

• 出版日期2011-2-1