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Modulation of signaling between TM4SF5 and integrins in tumor microenvironment

Cited 25 time in Web of Science Cited 26 time in Scopus
Authors

Lee, Sin-Ae; Park, Ki Hun; Lee, Jung Weon

Issue Date
2011-01
Publisher
Frontiers in Bioscience
Citation
Frontiers in Bioscience - Landmark, Vol.16, pp.1752-1758
Abstract
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 p27(kip1). 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.
ISSN
1093-9946
Language
English
URI
https://hdl.handle.net/10371/82066
DOI
https://doi.org/10.2741/3818
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