Integrative analysis of subcellular quantitative proteomics studies reveals functional cytoskeleton membrane-lipid raft interactions in cancer

Shah, Anup D., Inder, Kerry L., Shah, Alok K, Cristino, Alexandre S., McKie, Arthur B., Gabra, Hani, Davis, Melissa J. and Hill, Michelle M. (2016) Integrative analysis of subcellular quantitative proteomics studies reveals functional cytoskeleton membrane-lipid raft interactions in cancer. Journal of Proteome Research, 15 10: 3451-3462. doi:10.1021/acs.jproteome.5b01035


Author Shah, Anup D.
Inder, Kerry L.
Shah, Alok K
Cristino, Alexandre S.
McKie, Arthur B.
Gabra, Hani
Davis, Melissa J.
Hill, Michelle M.
Title Integrative analysis of subcellular quantitative proteomics studies reveals functional cytoskeleton membrane-lipid raft interactions in cancer
Journal name Journal of Proteome Research   Check publisher's open access policy
ISSN 1535-3907
1535-3893
Publication date 2016-10-07
Sub-type Article (original research)
DOI 10.1021/acs.jproteome.5b01035
Open Access Status Not yet assessed
Volume 15
Issue 10
Start page 3451
End page 3462
Total pages 12
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
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.
Keyword Cancer progression
Computational biology
Cytoskeleton
Lipid raft
Quantitative proteomics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
 
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