title: SQSTM1/p62 regulates the expression of junctional proteins through epithelial-mesenchymal transition factors.
abstract: The epithelial to mesenchymal transition (EMT) is an essential process during development and during tumor progression. Here, we observed the accumulation of the selective autophagy receptor and signaling adaptor sequestosome-1 (SQSTM1/p62) during growth factor-induced EMT in immortalized and tumor-derived epithelial cell lines. Modulation of the p62 level regulated the expression of junctional proteins. This effect was dependent on the ubiquitin-associated domain of p62, which stabilized the TGFβ/Smad signaling co-activator Smad4 and the EMT transcription factor Twist. This study highlights a novel function of p62 in a major epithelial phenotypic alteration.
authors.affiliation: a INSERM UMRS984 Châtenay-Malabry , France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Bertrand
authors.forename: Valérie
authors.initials: V
authors.lastname: Petit
authors.forename: Ashish
authors.initials: A
authors.lastname: Jain
authors.forename: Raymonde
authors.initials: R
authors.lastname: Amsellem
authors.forename: Terje
authors.initials: T
authors.lastname: Johansen
authors.forename: Lionel
authors.initials: L
authors.lastname: Larue
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
authors.forename: Isabelle
authors.initials: I
authors.lastname: Beau
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D002460:Cell Line; D004285:Dogs; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D051381:Rats; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050505:Mutant Proteins
keywords: EGF, epidermal growth factor; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IGF-II, insulin growth factor II; MDCK, Madin Darby Canine Kidney; NMuMG, Normal Murine Mammary Gland; SQSTM1, Sequestosome 1; TGFβ, Transforming Growth Factor β; autophagy; smad proteins; snail; twist; ubiquitin