Modulation of signaling between TM4SF5 and integrins in tumor microenvironment
- Lee, Sin-Ae; Park, Ki Hun; Lee, Jung Weon
- Issue Date
- FRONTIERS IN BIOSCIENCE INC
- FRONTIERS IN BIOSCIENCE-LANDMARK Vol.16 No.5, pp. 1752-1758
- 복합학; Cancer; Epithelial-Mesenchymal Transition; Hepatocarcinoma; Integrin; Microenvironment; TM4SF5; Review
- 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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