title: Modulation of signaling between TM4SF5 and integrins in tumor microenvironment.
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 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.
authors.affiliation: Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
authors.forename: Sin-Ae
authors.initials: SA
authors.lastname: Lee
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
authors.forename: Jung Weon
authors.initials: JW
authors.lastname: Lee
mesh_terms: D000199:Actins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D016023:Integrins / Q000502:physiology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D013449:Sulfonamides / Q000494:pharmacology; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: C540441:4'-(4-toluenesulfonylamido)-4-hydroxychalcone; D000199:Actins; D016023:Integrins; D008565:Membrane Proteins; D013449:Sulfonamides; C111029:TM4SF5 protein, human; D002599:Chalcone