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.