SQSTM1/p62 regulates the expression of junctional proteins through epithelial-mesenchymal transition factors

Cell Cycle. 2015;14(3):364-74. doi: 10.4161/15384101.2014.987619.


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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Autophagy
  • Cell Line
  • Dogs
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Intercellular Junctions / metabolism*
  • Mice
  • Mutant Proteins / metabolism
  • Protein Stability
  • Protein Structure, Tertiary
  • Rats
  • Signal Transduction


  • Adaptor Proteins, Signal Transducing
  • Mutant Proteins