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Issue 6, 2016
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Correlated S-palmitoylation profiling of Snail-induced epithelial to mesenchymal transition

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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

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Supplementary files

Article information


Submitted
08 Jan 2016
Accepted
18 Mar 2016
First published
18 Mar 2016

Mol. BioSyst., 2016,12, 1799-1808
Article type
Paper

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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