Open Access
Modulation of signaling between TM4SF5 and integrins in tumor microenvironment
Sin-Ae Lee1,Ki Hun Park1,Jung Weon Lee1
Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
DOI: 10.2741/3818 Volume 16 Issue 5, pp.1752-1758
Published: 01 January 2011

TM4SF5 is a transmembrane glycoprotein of the transmembrane 4 L six family, a branch of the tetraspanin family and highly expressed in many types of cancers. TM4SF5 induces epithelial-mesenchymal transition (EMT) by morphological changes resulting from inactivation of RhoA mediated by stabilized cytosolic p27kip1. TM4SF5-mediated EMT can lead to loss of contact inhibition and enhanced migration/invasion, presumably depending on cross-talks between TM4SF5 and integrins. An anti-TM4SF5 agent appears to target the second extracellular domain of TM4SF5, which is important for cross-talk with integrins, leading to a blockade of TM4SF5-mediated multilayer growth and migration/invasion. In addition, TM4SF5 engages in cross-talk with integrin alpha5 to induce and secrete VEGF, which in turn causes activation of angiogenesis in endothelial cells. Therefore, TM4SF5 plays a central regulatory role in a wide variety of physiological processes through cross-talk with integrins. This review presents current knowledge from in vitro and in vivo observations of the roles of TM4SF5-integrin cooperation in hepatocellular carcinogenesis and discusses important areas for future investigation.

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Sin-Ae Lee, Ki Hun Park, Jung Weon Lee. Modulation of signaling between TM4SF5 and integrins in tumor microenvironment. Frontiers in Bioscience-Landmark. 2011. 16(5); 1752-1758.