title: Tetraspanin TM4SF5 mediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma.
abstract: The growth of normal cells is arrested when they come in contact with each other, a process known as contact inhibition. Contact inhibition is lost during tumorigenesis, resulting in uncontrolled cell growth. Here, we investigated the role of the tetraspanin transmembrane 4 superfamily member 5 (TM4SF5) in contact inhibition and tumorigenesis. We found that TM4SF5 was overexpressed in human hepatocarcinoma tissue. TM4SF5 expression in clinical samples and in human hepatocellular carcinoma cell lines correlated with enhanced p27Kip1 expression and cytosolic stabilization as well as morphological elongation mediated by RhoA inactivation. These TM4SF5-mediated effects resulted in epithelial-mesenchymal transition (EMT) via loss of E-cadherin expression. The consequence of this was aberrant cell growth, as assessed by S-phase transition in confluent conditions, anchorage-independent growth, and tumor formation in nude mice. The TM4SF5-mediated effects were abolished by suppressing the expression of either TM4SF5 or cytosolic p27Kip1, as well as by reconstituting the expression of E-cadherin. Our observations have revealed a role for TM4SF5 in causing uncontrolled growth of human hepatocarcinoma cells through EMT.
authors: Cancer Research Institute, College of Medicine, Seoul National University, Jongno-gu, Seoul, Republic of Korea.
authors: Sin-Ae
authors: SA
authors: Lee
authors: Sung-Yul
authors: SY
authors: Lee
authors: Ik-Hyun
authors: IH
authors: Cho
authors: Min-A
authors: MA
authors: Oh
authors: Eun-Sil
authors: ES
authors: Kang
authors: Yong-Bae
authors: YB
authors: Kim
authors: Woo Duck
authors: WD
authors: Seo
authors: Suyong
authors: S
authors: Choi
authors: Ju-Ock
authors: JO
authors: Nam
authors: Mimi
authors: M
authors: Tamamori-Adachi
authors: Shigetaka
authors: S
authors: Kitajima
authors: Sang-Kyu
authors: SK
authors: Ye
authors: Semi
authors: S
authors: Kim
authors: Yoon-Jin
authors: YJ
authors: Hwang
authors: In-San
authors: IS
authors: Kim
authors: Ki Hun
authors: KH
authors: Park
authors: Jung Weon
authors: JW
authors: Lee
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication; D002460:Cell Line; D003260:Contact Inhibition; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C111029:TM4SF5 protein, human; C570858:TM4SF5 protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020742:rhoA GTP-Binding Protein