title: Proteasome inhibition causes epithelial-mesenchymal transition upon TM4SF5 expression.
abstract: Transmembrane 4 L six family member 5 (TM4SF5) is highly expressed in hepatocarcinoma and causes epithelial-mesenchymal transition (EMT) of hepatocytes. We found that TM4SF5-expressing cells showed lower mRNA levels but maintained normal protein levels in certain gene cases, indicating that TM4SF5 mediates stabilization of proteins. In this study, we explored whether regulation of proteasome activity and TM4SF5 expression led to EMT. We observed that TM4SF5 expression caused inhibition of proteasome activity and proteasome subunit expression, causing morphological changes and loss of cell-cell contacts. shRNA against TM4SF5 recovered proteasome expression, with leading to blockade of proteasome inactivation and EMT. Altogether, TM4SF5 expression appeared to cause loss of cell-cell adhesions via proteasome suppression and thereby proteasome inhibition, leading to repression of cell-cell adhesion molecules, such as E-cadherin.
authors.affiliation: Department of Biochemistry, School of Medicine, Cheju National University, Jeju 690-756, Korea. moonjcho@jejunu.ac.kr
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Jae Kook
authors.initials: JK
authors.lastname: Nam
authors.forename: Sin-Ae
authors.initials: SA
authors.lastname: Lee
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Lee
authors.forename: Somi K
authors.initials: SK
authors.lastname: Cho
authors.forename: Zee-Yong
authors.initials: ZY
authors.lastname: Park
authors.forename: Jung Weon
authors.initials: JW
authors.lastname: Lee
authors.forename: Moonjae
authors.initials: M
authors.lastname: Cho
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D057075:Enzyme Assays; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D054875:Ubiquitination; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D008565:Membrane Proteins; D061988:Proteasome Inhibitors; D011994:Recombinant Proteins; C111029:TM4SF5 protein, human; D051176:beta Catenin; D012313:RNA; D017228:Hepatocyte Growth Factor; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde