p62/Sequestosome 1 regulates transforming growth factor beta signaling and epithelial to mesenchymal transition in A549 cells.

Autor: Trelford CB; Schulich School of Medicine and Dentistry, Western University, Department of Physiology and Pharmacology, London, Ontario N6A 5B7, Canada., Ng E; Schulich School of Medicine and Dentistry, Western University, Department of Physiology and Pharmacology, London, Ontario N6A 5B7, Canada., Campbell CI; Schulich School of Medicine and Dentistry, Western University, Department of Physiology and Pharmacology, London, Ontario N6A 5B7, Canada., Di Guglielmo GM; Schulich School of Medicine and Dentistry, Western University, Department of Physiology and Pharmacology, London, Ontario N6A 5B7, Canada. Electronic address: john.diguglielmo@schulich.uwo.ca.
Jazyk: angličtina
Zdroj: Cellular signalling [Cell Signal] 2021 Sep; Vol. 85, pp. 110040. Date of Electronic Publication: 2021 May 14.
DOI: 10.1016/j.cellsig.2021.110040
Abstrakt: Transforming growth factor beta (TGFβ) receptor trafficking regulates many TGFβ-dependent cellular outcomes including epithelial to mesenchymal transition (EMT). EMT in A549 non-small cell lung cancer (NSCLC) cells has recently been linked to the regulation of cellular autophagy. Here, we investigated the role of the autophagy cargo receptor, p62/sequestosome 1 (SQSTM1), in regulating TGFβ receptor trafficking, TGFβ1-dependent Smad2 phosphorylation and EMT in A549 NSCLC cells. Using immunofluorescence microscopy, p62/SQSTM1 was observed to co-localize with TGFβ receptors in the late endosome. Small interfering RNA (SiRNA)-mediated silencing of p62/SQSTM1 resulted in an attenuated time-course of Smad2 phosphorylation but did not alter Smad2 nuclear translocation. However, p62/SQSTM1 silencing promoted TGFβ1-dependent EMT marker expression, actin stress fiber formation and A549 cell migration. We further observed that Smad4-independent TGFβ1 signaling decreased p62/SQSTM1 protein levels via a proteasome-dependent mechanism. Although p62/SQSTM1 silencing did not impede TGFβ-dependent autophagy, our results suggest that p62/SQSTM1 may aid in maintaining A549 cells in an epithelial state and TGFβ1 decreases p62/SQSTM1 prior to inducing EMT and autophagy.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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