title: Transmembrane 4 L Six Family Member 5 (TM4SF5)-Mediated Epithelial-Mesenchymal Transition in Liver Diseases.
abstract: The membrane protein TM4SF5, a member of the transmembrane 4L six family, forms a tetraspanin-enriched microdomain (TEM) on the cell surface, where many different membrane proteins and receptors form a massive protein-protein complex to regulate cellular functions including transdifferentiation, migration, and invasion. We recently reported that TM4SF5 causes epithelial-mesenchymal transition (EMT), eventually contributing to aberrant multilayer cellular growth, drug resistance, enhanced migration, invasion, its circulation in the blood, tumor initiation for successful metastasis, and muscle development in zebrafish. In this review, I summarize the information on the role of TM4SF5 in EMT-related functions at TM4SF5-enriched microdomain (T5EM) on cell surface, where proteins such as TM4SF5, CD151, CD44, integrins, and epidermal growth factor receptor (EGFR) can form numerous protein complexes. TM4SF5-mediated EMT contributes to diverse cellular functions, leading to fibrotic phenotypes and initiating and maintaining tumors in primary and/or metastatic regions, in addition to its role in muscle development in zebrafish. Anti-TM4SF5 strategies for addressing the protein networks can lead to regulation of the fibrotic, tumorigenic, and tumor-maintaining functions of TM4SF5-positive hepatic cells. This review is for us to (re)consider the antifibrotic or antitumorigenic (i.e., anti-EMT-related diseases) strategies of dealing with protein networks that would be involved in cross-talks to regulate various cellular functions during TM4SF5-dependent progression from fibrotic to cancerous hepatic cells.
authors.affiliation: Department of Pharmacy, Research Institute of Pharmaceutical Sciences, Tumor Microenvironment Global Core Research Center, Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul, Korea. Electronic address: jwl@snu.ac.kr.
authors.forename: Jung Weon
authors.initials: JW
authors.lastname: Lee
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000235:genetics / Q000503:physiopathology*; D008565:Membrane Proteins / Q000502:physiology*; D009132:Muscles / Q000196:embryology / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C111029:TM4SF5 protein, human
keywords: Development; EMT; Fibrosis; Metastasis; TM4SF5