Issue 6, 2016

Correlated S-palmitoylation profiling of Snail-induced epithelial to mesenchymal transition

Abstract

Epithelial cells form spatially-organized adhesion complexes that establish polarity gradients, regulate cell proliferation, and direct wound healing. As cells accumulate oncogenic mutations, these key tumor suppression mechanisms are disrupted, eliminating many adhesion complexes and bypassing contact inhibition. The transcription factor Snail is often expressed in malignant cancers, where it promotes transcriptional reprogramming to drive epithelial–mesenchymal transition (EMT) and establishes a more invasive state. S-Palmitoylation describes the fatty-acyl post-translational modification of cysteine residues in proteins, and is required for membrane anchoring, trafficking, localization and function of hundreds of proteins involved in cell growth, polarity, and signaling. Since Snail-expression disrupts apico-basolateral cell polarity, we asked if Snail-dependent transformation induces proteome-wide changes in S-palmitoylation. MCF10A breast cancer cells were retrovirally transduced with Snail and correlated proteome-wide changes in protein abundance and S-palmitoylation were profiled by using stable isotope labeling in cell culture with amino acid (SILAC) mass spectrometry. This analysis identified increased levels of proteins involved in migration, glycolysis, and cell junction remodeling, and decreased levels of proteins involved in cell adhesion. Overall, protein S-palmitoylation is highly correlated with protein abundance, yet for a subset of proteins, this correlation is uncoupled. These findings suggest that Snail-overexpression affects the S-palmitoylation cycle of some proteins, which may participate in cell polarity and tumor suppression.

Graphical abstract: Correlated S-palmitoylation profiling of Snail-induced epithelial to mesenchymal transition

Supplementary files

Article information

Article type
Paper
Submitted
28 ربيع الأول 1437
Accepted
09 جمادى الثانية 1437
First published
09 جمادى الثانية 1437

Mol. BioSyst., 2016,12, 1799-1808

Correlated S-palmitoylation profiling of Snail-induced epithelial to mesenchymal transition

J. L. Hernandez, D. Davda, J. D. Majmudar, S. J. Won, A. Prakash, A. I. Choi and B. R. Martin, Mol. BioSyst., 2016, 12, 1799 DOI: 10.1039/C6MB00019C

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