Integrative analysis of subcellular quantitative proteomics studies reveals functional cytoskeleton membrane–lipid raft interactions in cancer
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Lipid rafts are dynamic membrane microdomains that orchestrate molecular interactions and are implicated in cancer development. To understand the functions of lipid rafts in cancer, we performed an integrated analysis of quantitative lipid raft proteomics data sets modeling progression in breast cancer, melanoma, and renal cell carcinoma. This analysis revealed that cancer development is associated with increased membrane raft-cytoskeleton interactions, with ∼40% of elevated lipid raft proteins being cytoskeletal components. Previous studies suggest a potential functional role for the raft-cytoskeleton in the action of the putative tumor suppressors PTRF/Cavin-1 and Merlin. To extend the observation, we examined lipid raft proteome modulation by an unrelated tumor suppressor opioid binding protein cell-adhesion molecule (OPCML) in ovarian cancer SKOV3 cells. In agreement with the other model systems, quantitative proteomics revealed that 39% of OPCML-depleted lipid raft proteins are cytoskeletal components, with microfilaments and intermediate filaments specifically down-regulated. Furthermore, protein-protein interaction network and simulation analysis showed significantly higher interactions among cancer raft proteins compared with general human raft proteins. Collectively, these results suggest increased cytoskeleton-mediated stabilization of lipid raft domains with greater molecular interactions as a common, functional, and reversible feature of cancer cells.
Date Issued
2016-07-07
Date Acceptance
2015-11-10
Citation
Journal of Proteome Research, 2016, 15, pp.3451-3462
ISSN
1535-3893
Publisher
American Chemical Society
Start Page
3451
End Page
3462
Journal / Book Title
Journal of Proteome Research
Volume
15
Replaces
10044/1/46199
Copyright Statement
© 2016 American Chemical Society This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research after peer review and technical editing by the publisher. To access the final edited and published work see https://dx.doi.org/10.1021/acs.jproteome.5b01035
Subjects
cancer progression
computational biology
cytoskeleton
lipid raft
quantitative proteomics
Biochemistry & Molecular Biology
06 Biological Sciences
03 Chemical Sciences
Publication Status
Published