Integrative analysis of subcellular quantitative proteomics studies reveals functional cytoskeleton membrane-lipid raft interactions in cancer
Details
Publication Year 2016-09-02,Volume 15,Issue #10,Page 3451-3462
Journal Title
Journal of Proteome Research
Publication 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 approximately 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.
Publisher
ACS
Research Division(s)
Bioinformatics
PubMed ID
27384440
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2016-10-04 09:29:43
Last Modified: 2018-07-11 09:11:02
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